Supplementary Material
Systematic Meta-Analyses and Field Synopsis of Genetic Association Studies of Violence
and Aggression
Evangelos Vassos, MD, David A Collier, PhD, Seena Fazel, MD
Supplementary Material contents:
Supplementary Methods
Supplementary Table 1. Detailed description of studies included in the review
Supplementary Table 2. Grading of the strength of cumulative evidence of meta-analyses
with nominally positive findings according to the HuGENet criteria
Supplementary Figure 1. Forest Plots of meta-analyses of studies with categorical outcomes
Supplementary Figure 2. Forest Plots of meta-analyses of studies with continuous outcomes
Supplementary References
1
Supplementary Methods
Measures of aggression
In the categorical studies, cases were defined as individuals with a history of violence
including homicide, “offenders”, “criminals”, persons with antisocial personality disorder, or
people with history of aggression defined as a binary trait from the investigators of the
original studies. Controls were usually taken from the general population. When the study
reported two comparison groups, one with the same characteristics as the case group and the
other a sample of the general population, we selected the comparator on the basis of being
more similar to the cases (e.g. when aggressive alcoholics were compared with nonaggressive alcoholics and general population controls, we used the non-aggressive alcoholics
as the preferred comparison group) and so that findings were more related to associations
with violence rather than differences in the sample characteristics. Detailed description of the
sample characteristics and definition of aggression is given in Supplementary Table 1.
In the studies examining quantitative traits, aggression was measured with various scales or
questionnaires including the Buss-Durkee Hostility Inventory (BDHI),1 the Overt Aggression
Scale (OAS),2 the Brown-Goodwin Lifetime History of Aggression (BGHA),3 the Behavioral
Pathology in Alzheimer’s Disease (BEHAVE-AD),4 the Past Feelings and Acts of Violence
Scale (PFAVS),5 the Neuropsychiatric Inventory (NPI),6 the Child Behavior Checklist
(CBCL),7 the Revised Behavior Problem Checklist (RBPC),8 the Aggression Questionnaire
(AQ),9 the Life History of Aggression (LHA),10 and custom-made composite indexes of
aggression. Anger was measured in the majority of studies with State Trait Anger Expression
Inventory (STAXI)11 (for our analyses we used the trait anger scale) or with the angry
hostility facet of the NEO Personality Inventory.12
When more than one scale was used by the investigators, we agreed in advance on the order
of preference based on which scale more closely reflected the concept of externalized
aggression. We favored physical to verbal aggression, and direct to indirect forms. This
selection was blind to the direction of effect or the effect size of the association study. In the
case of questionnaires with various subscales, we selected either the overall scale or the
subscale that best reflected the previous concept. For example, in the case of BDHI we used
the “assault/irritability” subscale when available, otherwise the total scale, and in OAS, we
preferred the “physical aggression against other people” subscale.
Data management
The following data was extracted from each study: (i) allelic distribution and genotype
frequency when available in studies with categorical outcomes, (ii) numbers, mean scores,
and standard deviations (SD) of outcome by genotype in studies with continuous outcomes.
Additional data extracted for each study was year of publication, study country, sex
distribution, mean age, ethnic group, sample selection (general population, clinical, forensic
or other specific sample), and the outcome measurement used. When genotypic distribution,
means or standard deviations were not available for the preferred outcome measure, we
contacted the authors. In total, we identified 37 relevant studies with missing data and we
received tabular additional data from authors for 17 of those (46% response rate). This
response rate was almost complete for studies published since 2008.
2
Articles reporting more than one genetic marker were included as independent samples for
each marker. Similarly, publications that presented association results for males and females
separately or with any other division of the total sample (e.g. different ethnic groups) were
analyzed as independent samples.
Where associations of a particular polymorphism in the same or overlapping samples were
reported in separately published articles, we selected the publication with the larger sample.
If we were not certain about duplication of data, we contacted the corresponding authors of
both articles, and, in the absence of a response, when duplication was probable, we took the
conservative approach of excluding the smaller study.
When multiple identifiers were used for the same polymorphism, we used the most common
nomenclature and recorded the NCBI reference rs number where available. We examined our
dataset repeatedly to make sure that the order of alleles and genotypes was consistent across
our list. In the case of complete linkage disequilibrium (LD) of two single nucleotide
polymorphisms (SNPs) in the same gene (e.g. TPH1-A779C and TPH1-A218C), we pooled
the study estimates together as if they referred to the same marker. As MAOA gene is xlinked, we performed separate meta-analyses for males and females. For variable number of
tandem repeats (VNTR) polymorphisms with more than two variants (e.g. MAOA promoter
or DRD4-ex3), we analyzed high versus low activity alleles based on the grouping of
different number of repeats employed in each original study. Certain studies differed in the
characterization of rare alleles (e.g. 5 repeats in MAOA 30bpVNTR have been included in
either high or low activity markers). However as these variants are very rare, we assumed that
they made little difference in the overall association and hence included them in the
characterization presented in the original studies.
Statistical analyses
Studies with categorical and continuous outcomes of aggression were analyzed separately as
the first employed case-control designs while the second examined aggression in a sample as
a quantitative trait. For studies with binary outcomes, we tested allelic association (logadditive genetic model) and in studies with continuous outcomes we tested all 3 genetic
models (dominant, recessive and additive) when sufficient data were available. In order for a
polymorphism to be included in a meta-analysis, we required 3 or more separate samples to
examine the association of this polymorphism with aggression as a quantitative trait or with
violence as a binary outcome. The threshold of a minimum of 3 studies for the meta-analysis
was selected so that there were at least two replication attempts of the original finding.13
However, all the primary studies that met the inclusion criteria are reported (Supplementary
Table 1). Family-based association studies of related individuals were excluded. All
statistical analyses were performed with STATA statistical software, release 10 (Stata Corp.
2007) and the R Project for Statistical Computing (www.r-project.org).
Evidence of deviation from Hardy-Weinberg equilibrium (HWE) was assessed by χ2 tests
using the genotype frequencies of the sample analyzed in studies with continuous outcomes
or the control group in the case-control approach of studies with binary outcomes. For the
primary analyses, studies with HWE p-value <0.01 were excluded but we also performed
post hoc analyses with the inclusion of studies that deviated from HWE. In the case of the Xlinked MAOA genotype, when genotypes in females deviated from HWE, we also excluded
males from the meta-analysis as this may have been an indication of problems with
genotyping.
3
Studies that used both categorical and continuous outcome measures were included in the
meta-analyses. For the categorical studies we calculated study-specific allelic odds ratios
(ORs) and their 95% confidence intervals (CIs), with the exception of SLC6A3 where we
calculated genotypic OR under the dominant model (9 repeats carriers vs 10 repeats
homozygous) and DRD4-ex3 (presence of 7 repeats allele compared with all other
genotypes). For continuous data, we computed Cohen's d effect sizes and their standard error
(SE) from the reported means and SD. Whenever these data were not available, we computed
d directly from the reported statistic (t or p value). We analyzed both dominant and recessive
models by combining heterozygous with rare and common allele homozygous unless when
the investigators consistently reported only combined genotypes (i.e. in the case of DRD4ex3 or SLC6A3). To include analyses under the additive genetic model, which is more
consistent with the polygenic theory and with the allelic approach taken in the case-control
design, we estimated regression coefficients (β) and their SE from the given means and SD
for the 3 genotypes (method available from the authors upon request). Power for the most
commonly examined polymorphisms was calculated with the Genetic Power Calculator14
(http://pngu.mgh.harvard.edu/~purcell/gpc) using different ORs of 1.5, 1.2, and 1.1.
Initially, we calculated summary effect size and 95% CIs with the Der-Simonian and Laird
random effects model,15 a more conservative approach to pooling data which utilizes weights
that incorporate both the within and between study variance. This procedure was selected
because, due to the broad definition of the aggression outcomes and variability of the
samples, we expected large heterogeneity. Since a large number of analyses were performed,
p-values of <0.05 are presented only as indicative of potential significance.
We estimated between-study heterogeneity by calculating the Cochran’s Q and the I2 statistic
with its confidence intervals (CIs).16, 17 The latter incorporates the percentage of variation
across studies due to heterogeneity.18 As values of I2 > 50% are generally considered
indicative of large heterogeneity, we repeated the analysis with fixed effect models using the
Mantel-Haenszel weighting method when I2 were less than 50%. However, we favoured the
random effects method because both Q and I2 metrics carry considerable uncertainty when
few studies are included in a meta-analysis.19, 20
Sensitivity analyses
As we used a broad definition of aggression and samples were heterogeneous in relation to
baseline characteristics, we performed the following post-hoc analyses: (1) excluding nonEuropean and mixed ethnicity samples, (2) stratifying age groups (mean age<16, 16-65, and
>65 years old), (3) separate analysis of samples from the general population, clinical samples
with psychiatric disorder, offenders, and samples selected for substance use, (4) dividing the
outcomes by severity to anger, general measures of aggressiveness including antisocial
personality, history of violent acts, and criminal offending.
Assessment of epidemiological credibility
Evidence of publication bias was examined using Egger's, and Begg's tests21, 22 in studies
with continuous outcomes, and the modified version of Egger’s test23 in studies with a binary
outcome measure. For meta-analyses with nominally significant findings, the strength of
cumulative evidence was graded based on the Human Genome Epidemiology Network
(HuGENet) guidelines24 (Supplementary Table 2).
4
5
6
Supplementary Table 1. Detailed description of studies included in the review.25-211
Year
First author
Country
Ethnicity
Sample
description
Alcoholics (&
controls)
Alcohol and drug
users
Alcohol and drug
users & control
adolescents
Mean age
Sex
29.2/30.1
?
M/F
ratio
N/A
1992
Goldman
Finland
Caucasian
1994
Comings
USA
Caucasian
1995
Vanyukov
USA
?
1997
Strous
USA
1998
Sweet
1998
?
?
N/A
15.20
both
64/118
mixed
S inpatients
40.60
both
32/5
aggression
USA
Caucasian
73.00
both
93/182
Sweet
USA
Caucasian
73.00
both
93/182
1998
Sweet
USA
Caucasian
73.00
both
93/182
1998
Sweet
USA
Caucasian
Probable
Alzheimer's
Probable
Alzheimer's
Probable
Alzheimer's
Probable
Alzheimer's
73.00
both
93/182
physical
aggression
physical
aggression
physical
aggression
physical
aggression
1998
Lachman
USA
Caucasian
S patients
42.80
both
34/21
history of
violence
1998
Lappalainen
Finland
Caucasian
Alcoholic criminals,
family members,
controls
both
530/110
APD or IED &
alcoholism
1998
Lappalainen
USA
Indianamericans
Indian-american
tribe (no selection)
both
179/239
APD &
alcoholism
7
Measure
violence in
alcoholics
Ever jailed for
violence/ not
Conduct
disorder,
aggression
Instrument /
method
group
comparison
group
comparison
group
comparison
MPQ, CBCL
Polymorphism
rs
DRD2-Taq1A
rs1800497
N
(total)
46
DRD2-Taq1A
rs1800497
194
MAOA Intron 2
VNTR
rs10548363
182
records,
history group
comparison
CBRS group
comparison
CBRS group
comparison
CBRS group
comparison
CBRS group
comparison
COMTVal158Met
rs4680
37
DRD1-48A/G
rs4532
193
DRD2-C311G
rs1801028
DRD3-balI
rs6280
group
comparison
(records,
history)
group
comparison
(SCID to
diagnose APD
or IED)
group
comparison
(with SADS)
COMTVal158Met
rs4680
55
HTR1B-G861C
rs6296
280
HTR1B-G861C
rs6296
291
DRD4-ex3 48bp
VNTR
187
210
1998
Nielsen
Finland
Caucasian
Alcoholic violent
offenders, controls
PD patients
31.50
M
N/A
1998
New
USA
Caucasian
1998
Sander
Germany
1998
Mazzanti
1998
history of
violence
impulsivity,
aggression
APD in
alcoholics
group
comparison
BDHI, BIS
TPH1-A779C
rs1799913
511
?
M
N/A
TPH1-A218C
rs1800532
21
Caucasian
APD vs non-APD
alcoholics &
controls
?
both
?
group
comparison,
TPQ
5HTTLPR
rs4795541
315
Finland
Caucasian
Alcoholic criminal
offenders, controls
?
?
?
Offence &
alcoholism
5HTTLPR
rs4795541
397
59/41
(anger hostility)
group
comparison,
TPQ
NEO
Gelernter
USA
mixed
35.50
both
1999
Rotondo
Finland
Caucasian
32.00
M
1999
Huang
USA
?
Substance abuse,
pd, controls
Violent offenders vs
controls
brain tissue normal
& suicide
5HTTLPR
rs4795541
185
group
comparison
records,
history group
comparison
LHA, BDHI,
STAXI
group
comparison
TPH -6526
41.70
both
134/44
1999
Manuck
USA
mixed
normal
45.70
both
124/127
1999
Kotler
Israel
Caucasian
42.20
both
58/34
1999
Kotler
Israel
Caucasian
violent S vs nonviolent S (&
controls)
violent S vs nonviolent S (&
controls)
aggression,
anger
homicide
42.20
both
58/34
homicide
group
comparison
DRD4-ex3 48bp
VNTR
1999
Kotler
Israel
Caucasian
42.20
both
1999
Lappalainen
Finland
Caucasian
38.00
1999
Hallikainen
Finland
Caucasian
violent S vs nonviolent S (&
controls)
violent
alcoholics/controls
violent vs nonviolent alcoholics
(& controls)
58/34
homicide
group
comparison
5HTTLPR
rs4795541
82
M
N/A
HTR2CCys23Ser
5HTTLPR
436
N/A
group
comparison
group
comparison
rs6318
M
APD &
alcoholism
violent offence
& alcoholism
rs4795541
165
1999
Samochowie
c
Germany
Caucasian
APD vs non-APD
alcoholics &
controls
43.80
M
N/A
APD in
alcoholics
group
comparison
MAOA
promoter
30bpVNTR
8
history of
violence, arson
h of violence,
suicide
320
HTR1B-G861C
rs6296
78
TPH1-A218C
rs1800532
251
COMTVal158Met
rs4680
92
91
303
1999
Wei
UK
Caucasian
S patients
both
29/20
Violent behavior
1999
Ishiguro
Japan
Asian
antisocial alcoholics
(& non-antisocial)
/controls
2000
Nolan
USA
Caucasian
2000
Nolan
USA
2000
Nolan
2000
group
comparison
group
comparison
COMT (other)
49
5HTTLPR
[various
SNPs]
rs4795541
52.20
both
153/13
Antisocial
behavior &
alcoholism
S patients
?
M
N/A
history of
violence
history of
violence
history of
violence
group
comparison
group
comparison
group
comparison
TPH1-A779C
rs1799913
55
Caucasian
S patients
?
M
N/A
5HTTLPR
rs4795541
56
USA
Caucasian
S patients
?
M
N/A
Comings
USA
Caucasian
2 samples: students,
parents of twins
both
40/60
irritability
hostility
BADD,
BDHI, MPQ
ADRA2Apromoter
2000
Manuck
USA
Caucasian
normal
45.20
M
N/A
aggression
impulsivity
LHA, BIS,
BDHI
MAOA
promoter
30bpVNTR
110
2000
Persson
Sweden
Caucasian
normal
41.00
both
109/96
anger hostility
NEO
TH (TCAT)n
VNTR
58
2000
2000
Greenberg
Damberg
USA
Sweden
mixed
Caucasian
normal
normal
both
both
64/73
NEO
KSP
5HTTLPR
AP-2beta
902
137
30.4/54.6
M
N/A
both
174/182
COMTVal158Met
TPH1-A779C
329
30.16
rs1799913
350
UK
?
Suicide attempters
30.16
both
174/182
impulsiveness
USA
?
Probable
Alzheimer's
75.40
both
36/64
aggression
HTR2CCys23Ser
5HTTLPR
rs6318
Sweet
rs4795541
332
Holmes
UK
Caucasian
Probable
Alzheimer's
83.50
both
23/77
aggression
group
comparison
IVE impuls.
Quest, STAXI
IVE impuls.
Quest, STAXI
EBEHAVE,
ERS group
comparison
CAMDEX,
group
comparison
rs4680
?
violent alcoholics
vs controls
Suicide attempters
anger hostility
indirect
aggression
violent offence
& alcoholism
impulsiveness
rs4795541
?
2000
Hallikainen
Finland
Caucasian
2000
Evans
UK
2000
Evans
2001
2001
DRD1-48A/G
rs4532
105
9
MAOA
promoter
30bpVNTR
166
54
rs1800544
123
2001
Holmes
UK
Caucasian
Probable
Alzheimer's
83.50
both
23/77
aggression
CAMDEX,
group
comparison
BDHI
DRD3-balI
rs6280
2001
New
USA
mixed
PD patients
38.10
both
86/59
2001
Zalsman
Israel
Caucasian
17.40
both
40/48
2001
Jonsson
Sweden
Caucasian
adolescents patients
suicide attempters
healthy subjects
impulsive
aggression
violence
HTR1B-G861C
rs6296
145
PFAVS, IS
TPH1-A218C
rs1800532
88
42.90
both
185/152
aggression
KSP
AR_(CAG)n
rs72181988
335
2001
Reist
USA
?
40.80
M
N/A
2001
Zalsman
Israel
Caucasian
18.90
both
16/32
2001
Preuss
Germany
Caucasian
alcoholics and
controls
adolescents patients
suicide attempters
alcoholics
BIS, BGLHA,
BDHI
PFAVS, IS
5HTTLPR
rs4795541
27
5HTTLPR
rs4795541
46
107/28
aggression,
hostility
violence,
impulsivity
impulsivity
42.00
both
BIS
rs6311
135
both
94/104
h of violence
rs4680
198
both
102/31
APD in
alcoholics
group
comparison
group
comparison
HTR2A1438A/G
COMTVal158Met
5HTTLPR
2001
Liou
Taiwan
Asian
S patients
37.80
2001
Parsian
USA
Caucasian
APD vs non-APD
alcoholics &
controls
rs4795541
133
2001
Matsushita
Japan
Caucasian
2001
Twitchell
USA
Caucasian
2001
Jorm
Australia
Caucasian
alcoholics (&
controls)
children of
alcoholics
children &
adolescents
50.50
M
N/A
rs4795541
369
both
45/17
group
comparison
CBCL
5HTTLPR
10.90
5HTTLPR
rs4795541
62
16.00
both
?
RBPC, Rutter
PBQ
SLC6A340bpVNTR
680
normal
44.30
M
N/A
violence while
intoxicated
Aggressive
behavior
Conduct
disorder,
aggression
aggression
2002
Manuck
USA
mixed
LHA, (also
BDHI, BIS)
MAOA
promoter
30bpVNTR
58
2002
Rujescu
Germany
Caucasian
healthy/suicide
attempters
healthy
44.70
both
93/147
hostility, anger
BDHI, STAXI
TPH1-A779C
rs1799913
214
2002
Avramopoul
Greece
Caucasian
21.00
M
N/A
aggression
AQ
COMTVal158Met
rs4680
334
10
2002
Caspi
New
Zealand
Caucasian
young w or w/out
maltreatment
26.00
M
N/A
violence
2002
Patkar
USA
Black
36.60
both
75/30
2002
Patkar
USA
Black
36.60
both
75/30
2002
Staner
Caucasian
38.80
both
34/20
aggression,
impulsivity
aggression,
impulsivity
hostility
2002
Staner
35.20
both
11/16
hostility
2002
Saito
Luxembou
rg
Luxembou
rg
Finland
cocaine users (&
controls)
cocaine users (&
controls)
Impulsive inpatients
non-psychotic
Healthy controls
Caucasian
violent vs nonviolent alcoholics
(& controls)
M
N/A
violent offence
& alcoholism
2002
Hill
USA
Caucasian
Antisocial alcoholic
probands & parents
both
26/11
2002
Stoltenberg
USA
Caucasian
?
M
N/A
2002
Young
USA
?
Antisocial vs nonantisocial alcoholics
Children
7.00
both
?
2002
Kranzler
USA
Caucasian
substance
dependence +/ASPD (& controls)
2002
Kranzler
USA
Black
substance
dependence +/ASPD (& controls)
2002
Comings
USA
Caucasian
Substance abuse,
pd, controls
Caucasian
M
11
group
comparison,
convictions,
DTVS, APD
BDHI, SSS,
BIS, ASI
BDHI, SSS,
BIS, ASI
BIS, BDHI,
SADS
BIS, BDHI,
SADS
group
comparison
MAOA
promoter
30bpVNTR
MAOA
promoter
30bpVNTR
172
antisocial
behavior
ABC
HTTLPR, TPH,
HTR1b,
HTR2A,
HTR2C,
SLC6A4, MAOA
37
antisocial
behavior
Externalizing
behavior
APD
group
comparison
CBCL
5HTTLPR
APD
Aggression
5HTTLPR
442
rs4795541
5HTT-VNTR
105
103
TPH1-A218C
rs1800532
54
TPH1-A218C
rs1800532
27
rs4795541
33
SLC6A340bpVNTR
HTR1B-G861C
rs6296
278
group
comparison
HTR1B-G861C
rs6296
69
BDHI
AR_(GGC)n
group
comparison
790
121
2003
Berggård
Sweden
Caucasian
criminals/controls
35.00
M
N/A
violence
group
comparison
STAXI, group
comparison
LHA, group
comparison
LHA, group
comparison
LHA, group
comparison
HTR2A1438A/G
COMTVal158Met
COMTVal158Met
COMTVal158Met
MAOA
promoter
30bpVNTR
2003
Rujescu
Germany
Caucasian
44.00
both
202/275
aggression
2003
Strous
Israel
Caucasian
suicide attempters
& controls
S patients
M
N/A
aggression
2003
Strous
Israel
Caucasian
S patients
F
N/A
aggression
2003
Strous
Israel
Caucasian
S patients
M
N/A
aggression
2003
Strous
Israel
Caucasian
S patients
F
N/A
2003
Retz
Germany
Caucasian
offenders, various
diagnoses
34.70
M
2003
Westberg
Sweden
Caucasian
volunteers
42.00
2003
Koller
Germany
Caucasian
alcoholics (&
controls)
2003
Lu
Taiwan
Asian
2003
Cadoret
USA
2003
Sen
2004
aggression
LHA, group
comparison
MAOA
promoter
30bpVNTR
N/A
violence,
impulsiveness
DRD3-balI
F
N/A
ER-alpha VNTR
172
41.80
M
N/A
aggression,
irritability
aggression,
irritability
group
comparison
EIQ, WURS
KSP
BIS, BGLHA,
BDHI, group
comparison
MAOA
promoter
30bpVNTR
169
APD jailed/
controls (& nonAPD jailed)
30.00
M
N/A
APD jailed ±
alcoholism
group
comparison
MAOA
promoter
30bpVNTR
168
?
Adoptees
?
both
37/50
aggressivity
5HTTLPR
rs4795541
87
USA
Caucasian
Hypertensives
33.00
both
173/268
Hostility
Behavior
scales
NEO
rs6265
439
Han
Korea
Asian
M
N/A
aggression
OAS
rs4680
168
2004
Han
Korea
Asian
M
N/A
aggression
OAS
rs4795541
168
2004
Assal
USA
mixed
S patients (&
controls)
S patients (&
controls)
Alzheimer's
BDNFVal66Met
COMTVal158Met
5HTTLPR
both
37/59
agitation,
aggression
NPI
5HTTLPR
rs4795541
96
76.70
12
rs6311
317
rs4680
411
rs4680
94
rs4680
28
95
29
rs6280
146
2004
Assal
USA
mixed
Alzheimer's
76.70
both
37/59
NPI
HTR2A-T102C
rs6313
96
2004
Assal
USA
mixed
Alzheimer's
76.70
both
37/59
NPI
HTR2CCys23Ser
5HTT-VNTR
rs6318
96
2004
Assal
USA
mixed
Alzheimer's
76.70
both
37/59
2004
Retz
Germany
Caucasian
forensic referrals
(violent/no violent)
34.70
M
N/A
EIQ, WURS,
group
comparison
NPI group
comparison
NPI group
comparison
BIS, BGLHA,
BDHI
5HTTLPR
rs4795541
153
2004
Lam
China
Asian
Alzheimer's
77.40
both
2004
Craig
UK
?
Alzheimer's
78.00
both
139/257
2004
Huang
USA
mixed
mood disorders
37.60
M
N/A
agitation,
aggression
agitation,
aggression
aggression
HTR2A-T102C
rs6313
87
TPH1-A218C
rs1800532
396
MAOA
promoter
30bpVNTR
272
2004
Huang
USA
mixed
mood disorders
37.60
F
N/A
aggression
BIS, BGLHA,
BDHI
MAOA
promoter
30bpVNTR
398
2004
Volavka
USA
mixed
S patients
40.80
both
48/12
hostility
N/A
aggression
COMTVal158Met
MAOA
promoter
30bpVNTR
rs4680
M
PANSS
hostility item
BDHI,
forensic
examination
2004
Gerra
Italy
Caucasian
heroin users
(&controls)
33.70
2004
Gerra
Italy
Caucasian
heroin users
34.60
M
N/A
aggression
5HTTLPR
rs4795541
101
35.80
M
N/A
aggression
5HTTLPR
rs4795541
101
M
N/A
violence towards
self or others, or
violent threats
BDHI,
forensic
examination
BDHI,
forensic
examination
group
comparison
CABS,
PANSS, OAS
2004
Gerra
Italy
Caucasian
(controls)
2004
Koen
South
Africa
mixed
S patients
COMTVal158Met
rs4680
63
13
agitation,
aggression
agitation,
aggression
agitation,
aggression
violence
NPI
96
60
104
2004
Koen
South
Africa
mixed
S patients
M
N/A
violence
group
comparison
CABS,
PANSS, OAS
group
comparison
group
comparison
CD group
comparison
MAOA
promoter
30bpVNTR
2004
Liao
Taiwan
Asian
2004
Matsushita
Japan
Asian
2004
Foley
USA
Caucasian
violent
criminals/controls
alcoholics (&
controls)
Twins
34.70
M
N/A
violence
49.90
M
N/A
12.23
M
N/A
violence while
intoxicated
conduct disorder
2004
Zalsman
Israel
Caucasian
suicide attempters
17.70
both
29/40
2004
Zammit
UK
Caucasian
S patients (&
controls)
both
2004
Zammit
UK
Caucasian
S patients (&
controls)
2004
Zammit
UK
Caucasian
S patients (&
controls)
2004
Baca-Garcia
Spain
Caucasian
suicide attempters
only
2004
Baca-Garcia
Spain
Caucasian
suicide attempters
only
2004
Baca-Garcia
Spain
Caucasian
2004
Baca-Garcia
Spain
2005
Gerra
Italy
violence
PFAVS, IS
DRD4-ex3 48bp
VNTR
136/44
aggression
COMTVal158Met
M
N/A
aggression
overt
aggression
scale
overt
aggression
scale
MAOA
promoter
30bpVNTR
120
F
N/A
aggression
overt
aggression
scale
MAOA
promoter
30bpVNTR
42
36.80
M
N/A
Aggressive
behavior
5HTTLPR
rs4795541
63
36.80
F
N/A
Aggressive
behavior
5HTTLPR
rs4795541
139
controls only
M
N/A
Aggressive
behavior
5HTTLPR
rs4795541
87
Caucasian
controls only
F
N/A
Aggressive
behavior
5HTTLPR
rs4795541
77
Caucasian
heroin users
(&controls)
M
N/A
aggression
BGLAS, BIS,
group
comparison
BGLAS, BIS,
group
comparison
BGLAS, BIS,
group
comparison
BGLAS, BIS,
group
comparison
BDHI,
forensic
33.70
14
63
5HTTLPR
rs4795541
246
BDNFVal66Met
MAOA
promoter
30bpVNTR
rs6265
377
SLC6A340bpVNTR
514
67
rs4680
326
104
examination
2005
Chen
pathol aggressive
adolescents/super
controls/controls
?
aggression
violence
group
comparison?
SLC6A340bpVNTR
2005
Chen
pathol aggressive
adolescents/super
controls/controls
?
aggression
violence
group
comparison?
DRD2-Taq1A
rs1800497
41
2005
Tsai
Taiwan
Asian
violent
criminals/controls
violence
BDNFVal66Met
rs6265
283
2005
Jacob
Germany
Caucasian
PD/controls
history, MINI,
group
comparison
SCID II,
NEO-PI, TPQ
2005
Gerra
Italy
Caucasian
16.74
both
129/87
5HTTLPR
rs4795541
216
Reuter
Germany
Caucasian
25.43
both
125/127
personality,
aggressiveness
indirect hostility
BDHI, TPQ
2005
students (14-19) +/using drugs
normal
BDHI
TPH1-A779C
rs1799913
252
2005
Kweon
Korea
Asian
violent vs nonviolent alcoholics
(& controls)
45.70
M
N/A
violence
group
comparison
COMTVal158Met
rs4680
97
2005
Kweon
Korea
Asian
violent vs nonviolent alcoholics
(& controls)
45.70
M
N/A
violence
group
comparison
5HTTLPR
rs4795541
145
2005
Haberstick
USA
Caucasian
young w or w/out
maltreatment
?
M
N/A
conduct
problems
Lifetime
conduct
problems
MAOA
promoter
30bpVNTR
2005
Ha
Korea
Asian
Alzheimer's
74.90
both
27/38
aggression
5HTTLPR
2006
de Young
Canada
mixed
children
10.00
M
N/A
externalizing
behavior
BEHAVE-AD
group
comparison
informant
rating scales
34.70
M
N/A
both
15
PD cluster,
aggressiveness
41
MAOA
promoter
30bpVNTR
DRD4-ex3 48bp
VNTR
847
774
rs4795541
65
48
2006
de Young
Canada
mixed
adults with ADHD
35.17
M
N/A
externalizing
behavior
informant
rating scales
DRD4-ex3 48bp
VNTR
42
2006
de Young
Canada
mixed
boys
17.00
M
N/A
externalizing
behavior
informant
rating scales
DRD4-ex3 48bp
VNTR
87
2006
Eisenberger
USA
mixed
community sample
20.60
both
13/19
aggression
BSI,
Spielberger
anger trait
MAOA
promoter
30bpVNTR
32
2006
Sakai
USA
mixed
15.50
both
252/145
conduct disorder
with aggression
rs4795541
339
Giegling
Germany
Caucasian
40.00
both
173/243
anger aggression
CIDI, DISC,
group
comparison
STAXI, BDHI
5HTTLPR
2006
416
Widom
USA
mixed
41.00
both
268/141
violence
antisocial
behavior
HTR2A1438A/G
MAOA
promoter
30bpVNTR
rs6311
2006
adolescents w CD
& aggression
/controls
suicide attempters
& controls together
adults who had
been abused as
children and
controls
2006
Beitchman
Canada
?
aggressive
children/controls
9.54
both
70/12
aggression
5HTTLPR
rs4795541
2006
Beitchman
Canada
?
aggressive
children/controls
9.54
both
70/12
aggression
2006
Han
Korea
Asian
1st onset S
(&controls)
27.00
M
N/A
aggression
2006
Verona
USA
mixed
students
21.00
both
55/56
aggression
2006
Cheng
Taiwan
Asian
M
N/A
2006
Nilsson
Sweden
Caucasian
violent criminals
/controls
adolescents
19.00
M
N/A
violent criminal
activity
criminal activity
2006
Pritchard
UK
Caucasian
Alzheimer's
74.40
both
173/220
16
agitation,
aggression
composite
index:
criminal
history, selfreport, DIS
group
comparison
CBC, TRF
group
comparison
CBC, TRF
overt
aggression
scale
laboratory
experimet
group
comparison
criminality
index
NPI, group
comparison
409
5HTT-VNTR
318
146
COMTVal158Met
rs4680
132
5HTTLPR
rs4795541
111
AR_(CAG)n
rs72181988
254
MAOA
promoter
30bpVNTR
HTR2A-T102C
78
rs6313
393
2006
Pritchard
UK
Caucasian
Alzheimer's
74.40
both
173/220
agitation,
aggression
Aggressive
behavior
NPI, group
comparison
Parent and
teacher rating
scales
HTR2CCys23Ser
5HTTLPR
rs6318
393
2006
Haberstick
USA
Caucasian
School children
from general
population
9.50
both
358/374
rs4795541
732
2006
Sengupta
Canada
mixed
Children w ADHD
9.00
both
167/24
conduct disorder
191
N/A
Antisocial
behavior
COMTVal158Met
MAOA
promoter
30bpVNTR
rs4680
M
CD symptom
score
Antisocial
behavior scale
2006
Kim-Cohen
UK
Caucasian
Twins
7.00
2006
Huizinga
USA
Caucasian
Adolescents
M
N/A
Violence
MAOA
promoter
30bpVNTR
?
both
?
aggression
74.40
both
44/56%
74.40
both
44/56%
74.40
both
44/56%
both
1/1
both
1/1
17.00
F
N/A
aggression
irritability
aggression
irritability
aggression
irritability
violent
delinquency
violent
delinquency
criminal activity
composite
index:
criminal
history, selfreport, CD
DISC, group
comparison
NPI group
comparison
NPI group
comparison
NPI group
comparison
delinquency
scales
delinquency
scales
criminality
index
2007
Guerin
Canada
mixed
2007
Pritchard
UK
Caucasian
2007
Pritchard
UK
Caucasian
2007
Pritchard
UK
Caucasian
2007
Guo
USA
mixed
2007
Guo
USA
mixed
2007
Sjoberg
Sweden
Caucasian
aggressive children/
adult controls
Probable
Alzheimer's
Probable
Alzheimer's
Probable
Alzheimer's
adolescents (sibs &
twins!)
adolescents (sibs &
twins!)
adolescents
2007
Perlis
USA
Caucasian
depressed
39.20
both
42/52
anger expression
STAXI
parents of suicidal
probands, controls
48.00
both
49/51
anger-hostility
NEO
CREB1
(various)
TBX19
2007
Wasserman
Ukraine
Caucasian
17
975
277
BDNFVal66Met
ApoE (various)
rs6265
5HTTLPR
rs4795541
170
388
367
5HTT-VNTR
257
SLC6A340bpVNTR
DRD2-Taq1A
2530
rs1800497
MAOA
promoter
30bpVNTR
2525
115
[6 SNPs]
94
[various
SNPs]
744
2007
Sakai
USA
mixed
adolescents w CD
& aggression
/controls
forensic referrals
(violent/no violent)
16.09
both
48/52
conduct disorder
with aggression
CIDI, DISC,
group
comparison
group
comparison
5HTTLPR
2007
Reif
Germany
Caucasian
34.10
M
N/A
violence
2007
Reif
Germany
Caucasian
forensic referrals
(violent/no violent)
forensic referrals
(violent/no violent)
Suicide attempters,
& controls
Suicide attempters,
& controls
Suicide attempters,
& controls
Suicide attempters,
& controls
suicide completers
(& controls)
34.10
M
N/A
violence
5HTTLPR
anger aggression
group
comparison
group
comparison
STAXI, FAF
2007
Reif
Germany
Caucasian
34.10
M
N/A
violence
2007
Gietl
Germany
Caucasian
?
both
198/283
2007
Serretti
Germany
Caucasian
?
both
anger aggression
STAXI, FAF
2007
Serretti
Germany
Caucasian
?
both
anger aggression
2007
Giegling
Germany
Caucasian
?
both
198/283
2007
Zouk
Canada
Caucasian
38.00
both
274/64
2007
Frazzetto
Italy
Caucasian
psychiatric
outpatients, controls
32.18
M
2007
Frazzetto
Italy
Caucasian
psychiatric
outpatients, controls
32.18
2007
2007
Silva
Fresan
Chile
Mexico
mixed
?
Borderline PD
schizophrenic
patients
2007
Fresan
Mexico
?
schizophrenic
patients
rs4795541
MAOA
promoter
30bpVNTR
SLC6A340bpVNTR
ABCG1
1736
184
rs4795541
184
184
[5 SNPs]
414
rs6318
404
STAXI, FAF
HTR2CCys23Ser
HTR1A
rs6295
404
anger aggression
STAXI, FAF
TACR1
[4 SNPs]
BDHI, BIS,
BGHA
HTR1B-G861C
rs6296
N/A
Aggression
(proxy
interview)
aggression
aggression
questionnaire
MAOA
promoter
30bpVNTR
82
F
N/A
aggression
aggression
questionnaire
MAOA
promoter
30bpVNTR
153
?
30.50
both
both
13/36
22/49
aggression
aggression
OAS
group
comparison &
OAS
5HTTLPR
DRD4-ex3 48bp
VNTR
30.50
M
N/A
aggression
group
comparison &
OAS
MAOA
promoter
30bpVNTR
18
rs4795541
322
49
71
49
2007
Fresan
Mexico
?
schizophrenic
patients
30.50
F
N/A
aggression
group
comparison &
OAS
MAOA
promoter
30bpVNTR
22
2007
Yang
Korea
Asian
Students
22.80
F
N/A
anger
STAXI
MAOA
promoter
30bpVNTR
211
2007
Flory
USA
Caucasian
?
both
76/36
Hostility
BDHI
2007
Nobile
Italy
Caucasian
12.11
both
309/298
CBCL
Nobile
Italy
Caucasian
12.11
both
309/298
Aggressive
behavior
Aggressive
behavior
COMTVal158Met
5HTTLPR
2007
Personality
disorders
general population
preadolescents
general population
preadolescents
CBCL
DRD4-ex3 48bp
VNTR
2007
Gerra
Italy
Caucasian
22.60
M
N/A
aggressiveness
BDHI
5HTTLPR
2008
Schulz-Heik
USA
mixed
15.80
both
?
conduct disorder
group
comparison
SLC6A340bpVNTR
2008
Keltikangas
Finland
Caucasian
cocaine users (&
controls)
adolescents w CD
& substance
/controls
healthy population
28.00
both
313/416
hostility
HTR1A
rs6295
729
2008
Keltikangas
Finland
Caucasian
healthy population
28.00
both
313/416
hostility
HTR2A-T102C
rs6313
729
2008
Rujescu
Germany
Caucasian
?
both
198/283
anger aggression
NOS1
[4 SNPs]
571
2008
Kang
Korea
Asian
Suicide attempters,
& controls
Students
anger,
cynicism,
paranoia
scales
anger,
cynicism,
paranoia
scales
STAXI, FAF
22.50
M
N/A
anger
STAXI, TFS
DRD4-ex3 48bp
VNTR
184
2008
Kang
Korea
Asian
Students
22.50
F
N/A
anger
STAXI, TFS
DRD4-ex3 48bp
VNTR
124
2008
Kang
Korea
Asian
Students
22.50
M
N/A
anger
STAXI, TFS
COMTVal158Met
19
rs4680
112
rs4795541
589
589
rs4795541
96
303
rs4680
184
2008
Kang
Korea
Asian
Students
22.50
F
N/A
anger
STAXI, TFS
2008
Guo
USA
mixed
adolescents (sibs &
twins!)
15.60
M
N/A
violent
delinquency
delinquency
scales
2008
Guo
USA
mixed
adolescents (sibs &
twins!)
15.50
F
N/A
violent
delinquency
delinquency
scales
MAOA
promoter
30bpVNTR
2008
Caspi
UK
Caucasian
9.20
both
214/27
UK
Caucasian
9.20
both
214/27
2008
Caspi
UK
Caucasian
9.20
both
214/27
COMTVal158Met
SLC6A340bpVNTR
DRD4-ex3 48bp
VNTR
rs4680
Caspi
conduct
problems
conduct
problems
conduct
problems
CAPA
2008
ADHD children
(Cardiff)
ADHD children
(Cardiff)
ADHD children
(Cardiff)
2008
Caspi
UK
Caucasian
7.00
both
UK
Caucasian
7.00
both
1839
Caspi
UK
Caucasian
7.00
both
2008
Caspi
UK
Caucasian
ADHD children (Erisk)
controls (E-risk)
7.00
both
2008
Caspi
UK
Caucasian
ADHD children (Erisk)
7.00
both
COMTVal158Met
COMTVal158Met
SLC6A340bpVNTR
SLC6A340bpVNTR
DRD4-ex3 48bp
VNTR
rs4680
2008
Child behavior
checklist
Child behavior
checklist
Child behavior
checklist
Child behavior
checklist
Child behavior
checklist
185
Caspi
Aggressive
behavior
Aggressive
behavior
Aggressive
behavior
Aggressive
behavior
Aggressive
behavior
rs4680
2008
ADHD children (Erisk)
controls (E-risk)
2008
Caspi
UK
Caucasian
controls (E-risk)
7.00
both
Aggressive
behavior
Child behavior
checklist
DRD4-ex3 48bp
VNTR
2008
Caspi
New
Zealand
Caucasian
ADHD children
(Dunedin)
26.00
both
Antisocial
behavior, adult
court convictions
Antisocial
composite
index, group
comparison
COMTVal158Met
20
CAPA
CAPA
COMTVal158Met
MAOA
promoter
30bpVNTR
rs4680
124
1200
1324
241
186
184
180
1788
184
1803
rs4680
49
2008
Caspi
New
Zealand
Caucasian
controls (Dunedin)
26.00
both
Antisocial
behavior, adult
court convictions
2008
Caspi
New
Zealand
Caucasian
ADHD children
(Dunedin)
26.00
both
Antisocial
behavior, adult
court convictions
2008
Caspi
New
Zealand
Caucasian
controls (Dunedin)
26.00
both
Antisocial
behavior, adult
court convictions
2008
Caspi
New
Zealand
Caucasian
ADHD children
(Dunedin)
26.00
both
Antisocial
behavior, adult
court convictions
2008
Caspi
New
Zealand
Caucasian
controls (Dunedin)
26.00
both
Antisocial
behavior, adult
court convictions
2008
Rajender
India
Caucasian
criminals/controls
2008
Giegling
Germany
Caucasian
2008
Kulikova
Russia
Caucasian
Suicide attempters,
& controls
Young women
2008
Hong
Korea
Asian
2008
Burt
USA
2008
Burt
2008
Ducci
M
N/A
43.20
both
196/283
17.00
F
N/A
Schizophrenic
patients
?
M
N/A
Caucasian
Students
19.00
M
N/A
USA
Caucasian
Students
19.00
M
N/A
USA
Indianamericans
Indian-american
tribe (alcoholics +/APD & controls)
37.80
F
N/A
21
serious offence
(rape, murder)
anger aggression
Aggressive
behavior
homicide
Aggressive
behavior
Aggressive
behavior
APD in
alcoholism
Antisocial
composite
index, group
comparison
Antisocial
composite
index, group
comparison
Antisocial
composite
index, group
comparison
Antisocial
composite
index, group
comparison
Antisocial
composite
index, group
comparison
group
comparison
STAXI, FAF
COMTVal158Met
Buss-Darky?
group
comparison,
OAS, LHA
ASR
rs4680
787
SLC6A340bpVNTR
48
SLC6A340bpVNTR
727
DRD4-ex3 48bp
VNTR
49
DRD4-ex3 48bp
VNTR
799
AR_(CAG)n
rs72181988
645
ESR1
[6 SNPs]
?
COMTVal158Met
COMTVal158Met
rs4680
114
rs4680
193
ASR
SLC6A340bpVNTR
TPH1-A218C
group
comparison
(of ASPD)
MAOA
promoter
30bpVNTR
197
rs1800532
204
167
2008
Gonzalez
Cuba
mixed
Students & staff
both
24/76
Aggression
KSP
2008
Kim
Korea
Asian
S patients (&
controls)
2008
Pombo
Portugal
Caucasian
2009
Gonda
Hungary
2009
Tikkanen
2009
CYP2D6
(various)
COMTVal158Met
[various
SNPs]
rs4680
246
38.40
both
96/69
Aggressive
behavior
Alcohol dependent
48.00
both
78/19
Caucasian
Healthy volunteers
32.13
F
N/A
Finland
Caucasian
alcoholic criminals
32.50
M
N/A
outward
aggression
aggression,
hostility
Impulsive
violence
group
comparison,
OAS
SDAS
5HTTLPR
rs4795541
97
BDHI
5HTTLPR
rs4795541
169
examination
MAOA
promoter
30bpVNTR
Sysoeva
Russia
Caucasian
13.00
F
N/A
2009
Sysoeva
Russia
Caucasian
23.00
F
N/A
2009
Sysoeva
Russia
Caucasian
13.00
F
N/A
2009
Reif
Germany
Caucasian
Young women,
controls
Young women,
controls
Young women,
swimmers
forensic referrals
(violent/no violent)
Aggressive
behavior
Aggressive
behavior
Aggressive
behavior
Violence
BDHI
5HTTLPR
rs4795541
64
BDHI
5HTTLPR
rs4795541
40
BDHI
5HTTLPR
rs4795541
62
34.10
M
N/A
group
comparison
NOS1 Ex1f
VNTR
182
2009
McDermott
USA
mixed
Students
22.00
M
N/A
Aggressive
tendencies
controlled
experiment
MAOA
promoter
30bpVNTR
70
2009
Williams
Australia
Caucasian
Healthy individuals
36.34
M
N/A
Antisocial index
NEO
MAOA
promoter
30bpVNTR
140
2009
Williams
Australia
Caucasian
Healthy individuals
35.80
F
N/A
Antisocial index
NEO
MAOA
promoter
30bpVNTR
68
2009
2009
2009
Terraciano
Terraciano
Conner
Italy
USA
USA
Caucasian
mixed
Caucasian
volunteers
volunteers
Students
42.60
52.90
18.70
both
both
both
43/57
49/51
168/193
anger-hostility
anger-hostility
Hostility
questionnaire
NEO
NEO
controlled
experiment
5HTTLPR
5HTTLPR
HTR1B-G861C
22
167
174
rs4795541
rs4795541
rs6296
3913
548
361
2009
Kinnally
USA
mixed
mood disorders &
controls
38.60
F
N/A
Hostility
aggressiveness
BGAI, BIS,
BDHI
MAOA
promoter
30bpVNTR
2009
Kim
Korea
Asian
Schizophrenic
patients
38.20
both
56/47
aggression,
anger
5HTTLPR
rs4795541
2009
Kim
Korea
Asian
Schizophrenic
patients
38.20
both
5HTTLPR
rs4795541
2009
Gu
China
Asian
36.00
M
N/A
Violent behavior
584
Wagner
Germany
Caucasian
33.00
both
49/110
rs6265
159
2009
Wagner
Germany
Caucasian
Borderline PD
32.00
F
N/A
impulsive
aggression
impulsive
aggression
COMTVal158Met
BDNFVal66Met
COMTVal158Met
rs4680
2009
Schizophrenic
patients
Borderline PD
MOAS,
STAXI, group
comparison
MOAS,
STAXI, group
comparison
MOAS, group
comparison
BDHI
rs4680
161
2009
Edwards
USA
Caucasian
School children
from general
population
M
N/A
externalizing
behavior
Child behavior
checklist
MAOA
promoter
30bpVNTR
2009
Perroud
France
?
Suicide attempters
39.60
both
30/70
Anger
STAXI
rs4680
779
2009
2009
Perroud
Perroud
France
France
?
?
Suicide attempters
Suicide attempters
39.60
39.60
both
both
30/70
30/70
Anger
Anger
STAXI
STAXI
COMTVal158Met
5HTTLPR
TPH1-A218C
rs4795541
rs1800532
835
840
2009
Perroud
France
?
Suicide attempters
39.60
both
30/70
Anger
STAXI
rs6311
562
2009
Perroud
France
?
Suicide attempters
39.60
M
N/A
Anger
STAXI
HTR2A1438A/G
MAOA
promoter
30bpVNTR
2009
Perroud
France
?
Suicide attempters
39.60
F
N/A
Anger
STAXI
MAOA
promoter
30bpVNTR
2009
Perroud
France
?
Suicide attempters
39.60
both
30/70
Anger
STAXI
BDNFVal66Met
23
aggression,
anger
BDHI
159
103
186
248
590
rs6265
842
2009
Perroud
France
?
Suicide attempters
39.60
both
30/70
Anger
STAXI
HTR1B-G861C
rs6296
839
2009
Kim
Korea
Asian
Schizophrenic
patients
38.20
both
57/47
aggression,
anger
TPH1-A218C
rs1800532
104
2009
Hohmann
Germany
Caucasian
Adolescents
15.00
both
144/154
5HTTLPR
rs4795541
298
2009
Hohmann
Germany
Caucasian
Adolescents
15.00
both
144/154
externalizing
behavior
externalizing
behavior
group
comparison,
OAS, STAXI
YSR, CBCL
YSR, CBCL
DRD4-ex3 48bp
VNTR
2009
Zimmerman
Germany
Caucasian
Adolescents
12.00
both
45/46
aggressiveness
5HTTLPR
2009
May
USA
Caucasian
Intellectual
disabilities (&
controls)
41.00
M
N/A
Problem
behavior
CCQ (mothers
report)
group
comparison, N
of PB
2009
Jensen
USA
Caucasian
Students
18.60
both
rs13212041
359
Westberg
Sweden
Caucasian
volunteers
59.00
M
N/A
Conduct
disorder items
KSP, TCI
HTR1B
2009
AR_(CAG)n
rs72181988
141
2009
Westberg
Sweden
Caucasian
35.00
M
N/A
KSP, TCI
AR_(CAG)n
rs72181988
63
2010
Isir
Turkey
Caucasian
13.50
both
45/27
group
comparison
COMTVal158Met
rs4680
72
2010
Kim
Korea
Asian
forensic patients
with violent history
Violent offenders
with MR vs
controls
S patients (&
controls)
Conduct disorder
items
nonconformity
factor (KSP)
nonconformity
factor (KSP)
violent offence
38.40
both
96/69
aggression,
anger
TPH1-A218C
rs1800532
165
2010
Beaver
USA
mixed
adolescents
16.47
M
N/A
gang
membership,
weapon use
group
comparison,
OAS, STAXI
group
comparison
MAOA
promoter
30bpVNTR
1041
2010
Beaver
USA
mixed
adolescents
16.47
F
N/A
gang
membership,
weapon use
group
comparison
MAOA
promoter
30bpVNTR
1155
2010
Dmitrieva
Russia
Caucasian
adolescents
14.60
both
50/50
Delinquency
Problem
behavior scale
& offending
DRD4-ex3 48bp
VNTR
235
24
298
rs4795541
MAOA
promoter
30bpVNTR
91
70
checklist
2010
USA
Caucasian
PD and controls
42.00
both
70/53
Aggression
2010
PerezRodriguez
Chung
BDHI, BPAQ,
OAS
group
comparison,
LHA, OAS
Cook-Medley,
Buss-Perry,
HDHQ
TPH2
Korea
Asian
violent vs nonviolent S patients
38.00
M
N/A
homicide
2010
Williams
USA
mixed
Healthy volunteers
34.20
M
N/A
Hostility
2010
2010
Yang
Albaugh
Korea
USA
Asian
?
Students
Children
23.00
11.00
F
both
N/A
97/69
Anger
Aggressive
behavior
Problem
behavior
STAXI
Child behavior
checklist
group
comparison, N
of PB
5HTTLPR
COMTVal158Met
5HTTLPR
2010
May
USA
Caucasian
Intellectual
disabilities (&
controls)
41.00
M
N/A
2010
May
USA
Caucasian
Intellectual
disabilities (&
controls)
41.00
M
N/A
Problem
behavior
group
comparison, N
of PB
5HTT-VNTR
2010
Grigorenko
Russia
Caucasian
Adolescents
16.20
M
N/A
Incancerated
offenders vs
controls
group
comparison
COMTVal158Met
rs4680
461
2011
Koh
Korea
Asian
Violent S &
controls
34.00
both
138/94
criminal activity
COMTVal158Met
rs4680
229
34.00
both
138/94
criminal activity
group
comparison,
LHA
group
comparison,
LHA
group
comparison
2011
Koh
Korea
Asian
Violent S &
controls
TPH1-A218C
rs1800532
230
2011
Kasiakogia
UK
?
Alcoholics with
criminal record (&
controls)
DRD2-Taq1A
rs1800497
1006
2011
Vogel
Germany
Caucasian
BPD patients &
controls
group
comparison,
BDHI
AVPR1A
criminal police
record
33.20
both
25
95/223
impulsive
aggression
BDNFVal66Met
123
rs6265
MAOA
promoter
30bpVNTR
95
86
rs4795541
rs4680
228
149
rs4795541
67
63
318
2011
Johansson
Finland
Caucasian
University students
administered
alcohol or placebo
22.70
M
N/A
Aggressive
behavior
laboratory
paradigm
OXTR
116
2011
Fergusson
New
Zealand
mixed
birth cohort - not
exposed to abuse
30.00
M
N/A
Violent offences
self-report,
police, SCL90
MAOA
promoter
30bpVNTR
309
2011
Fergusson
New
Zealand
mixed
birth cohort exposed to abuse
30.00
M
N/A
Violent offences
self-report,
police, SCL90
MAOA
promoter
30bpVNTR
89
2011
2011
2011
Gonda
Gonda
Tosato
Hungary
Hungary
Italy
Caucasian
Caucasian
Caucasian
depressed
controls
S patients
48.00
32.00
42.10
F
F
both
N/A
N/A
41/39
Spain
Caucasian
M
N/A
rs72181988
153
2011
Aluja
Spain
Caucasian
Inmates (& vs
controls)
controls
5HTTLPR
5HTTLPR
COMTVal158Met
AR_(CAG)n
137
118
80
Aluja
M
N/A
AR_(CAG)n
rs72181988
108
2011
Brennan
Australia
Caucasian
birth cohort
both
43/57
BDHI
BDHI
OAS, group
comparison
Zuckerman
questionnaire
Zuckerman
questionnaire
ABCL, ASR
rs4795541
rs4795541
rs4680
2011
Aggression
Aggression
Aggression
against others
aggression
hostility
aggression
hostility
Aggression
rs4680
430
2011
Reti
USA
mixed
cohort
both
224/211
antisocial
behavior
ASPD, NEO
COMTVal158Met
MAOA
promoter
30bpVNTR
2011
Zai
Canada
mixed
10.80
both
104/40
>90 percentile of
aggression
CBC & TRF
SLC6A340bpVNTR
2011
Zai
Canada
mixed
10.80
both
104/40
>90 percentile of
aggression
CBC & TRF
DRD2-Taq1A
2011
Zai
Canada
mixed
10.80
both
104/40
>90 percentile of
aggression
CBC & TRF
DRD4-ex3 48bp
VNTR
2011
Hurd
Canada
mixed
children with
pervasive
aggression vs
controls
children with
pervasive
aggression vs
controls
children with
pervasive
aggression vs
controls
psychology students
19.20
M
N/A
physical
aggression
AQ
AR_(CAG)n
20.00
26
435
260
rs1800497
282
256
rs72181988
2011
Hurd
Canada
mixed
psychology students
19.20
M
2011
Zalsman
Israel
Caucasian
suicidal and not
suicidal adolescents
16.00
both
2011
Nedic
Croatia
Caucasian
suicidal alcoholics
49.50
M
N/A
2011
Nedic
Croatia
Caucasian
49.50
M
N/A
2011
Nedic
Croatia
Caucasian
not suicidal
alcoholics
suicidal alcoholics
51.50
F
N/A
2011
Nedic
Croatia
Caucasian
51.50
F
N/A
2011
Basoglu
Turkey
Caucasian
not suicidal
alcoholics
offenders with APD
& controls
21.00
M
N/A
2011
Cao
China
Asian
Children exposed to
domestic violence
14.50
both
Aggressive
behavior
2011
Cao
China
Asian
Children exposed to
domestic violence
14.50
both
Aggressive
behavior
27
N/A
physical
aggression
AQ
MAOA
promoter
30bpVNTR
Anger, Impulse
control
ICS, Anger
inventory
HTR2A,
5HTTLPR,
MAO-A
Aggressive
behavior
Aggressive
behavior
Aggressive
behavior
Aggressive
behavior
offending
behavior
BGLHA
COMTVal158Met
COMTVal158Met
COMTVal158Met
COMTVal158Met
SNAP25 DdeI
rs4680
59
rs4680
253
rs4680
23
rs4680
58
COMTVal158Met
rs4680
68
5HTTLPR
rs4795541
68
BGLHA
BGLHA
BGLHA
group
comparison,
Psychopathy
group
comparison,
CBC
group
comparison,
CBC
211
129
Supplementary Table 2. Grading of the strength of cumulative evidence of meta-analyses with nominally positive findings according to the HuGENet
criteria.
Gene
Subgroup*
Model
Studies with categorical outcomes
COMT
Violence
allelic
MAOA-M Violence
allelic
TPH1
Psychiatric patients allelic
Studies with continuous outcomes
5HTTLPR Age >16 and <65
dominant
5HTTLPR Substance users
dominant
COMT
Caucasian
recessive
COMT
Substance users
recessive
COMT
Anger
recessive
COMT
Caucasian
additive
COMT
Substance users
additive
MAOA-F
Aggressiveness
recessive
N
AMOUNT
N minor
REPLICATION
I2
BIAS
Publ. Bias
OVERALL
6
3
4
B
B
B
344
629
772
C
A
A
54
0
16
C
A
B
Harbord p=0.047
C
B
B
22
4
16
4
5
16
4
4
A
B
A
B
A
A
B
B
9742
599
4933
378
1355
4933
378
263
B
B
C
A
A
C
A
A
39
28
56
12
0
54
0
0
C
C
B
B
B
B
B
B
Egger p = 0.044
Egger p = 0.027
C
C
C
B
B
C
B
B
* Subgroup analyses were performed by ethnicity, age of participants, sample characteristics, and outcome measure.
N is the number of studies included, N minor, the size of the smallest genetic group (minor allele), I 2 = I square test for heterogeneity and Publ. bias = the method and
the p-value of publication bias (when significant). The overall evidence was rated as A (strong), B (moderate) or C (weak).
28
29
Supplementary Figure 1. Forest Plots of meta-analyses of studies with categorical outcomes
5HT-1B-G861C
1. By ethnicity (1 caucasian, 0 other)
Odds ratio
(95% CI)
Study
0
Lappalainen
1.14 ( 0.76, 1.70)
Huang
1.46 ( 0.65, 3.26)
Kranzler
0.50 ( 0.22, 1.14)
Subtotal
0.99 ( 0.58, 1.67)
1
Lappalainen
0.58 ( 0.38, 0.87)
Kranzler
0.98 ( 0.61, 1.56)
Subtotal
0.74 ( 0.44, 1.24)
Overall
0.86 ( 0.60, 1.24)
.219419
1
Odds ratio
4.55747
4. By outcome measure
Odds ratio
(95% CI)
Study
Aggresiveness
Lappalainen
0.58 ( 0.38, 0.87)
Lappalainen
1.14 ( 0.76, 1.70)
Kranzler
0.50 ( 0.22, 1.14)
Kranzler
0.98 ( 0.61, 1.56)
Subtotal
0.79 ( 0.54, 1.17)
Violence
Huang
1.46 ( 0.65, 3.26)
Subtotal
1.46 ( 0.65, 3.26)
Overall
0.86 ( 0.60, 1.24)
.219419
1
Odds ratio
30
4.55747
5HTTLPR
1. By ethnicity (1: caucasian, 0: other)
Odds ratio
(95% CI)
Study
0
Ishiguro
Sweet
Liao
Ha
Sakai
Beitchman
Kim
Cao
Subtotal
1.48 ( 0.84, 2.63)
1.65 ( 1.19, 2.30)
0.83 ( 0.56, 1.23)
0.59 ( 0.26, 1.36)
0.46 ( 0.32, 0.66)
0.79 ( 0.58, 1.09)
1.48 ( 0.77, 2.82)
1.28 ( 0.59, 2.78)
0.97 ( 0.68, 1.39)
1
Sander
Mazzanti
Kotler
Nolan
Matsushita
Stoltenberg
Retz
Gerra
May
Parsian
Pritchard
Subtotal
0.92 ( 0.62, 1.36)
0.99 ( 0.75, 1.31)
0.69 ( 0.36, 1.32)
0.59 ( 0.28, 1.25)
0.65 ( 0.35, 1.20)
0.89 ( 0.33, 2.42)
0.56 ( 0.35, 0.88)
0.51 ( 0.29, 0.89)
2.51 ( 0.85, 7.42)
1.35 ( 0.81, 2.25)
1.16 ( 0.78, 1.72)
0.85 ( 0.68, 1.07)
Overall
0.90 ( 0.74, 1.09)
.134688
1
Odds ratio
7.42452
2. By Age (1: <16, 2: 16-65, 3: >65)
Odds ratio
(95% CI)
Study
agegroup==1
Beitchman
0.79 ( 0.58, 1.09)
Cao
1.28 ( 0.59, 2.78)
Subtotal
0.88 ( 0.60, 1.31)
agegroup==2
Ishiguro
1.48 ( 0.84, 2.63)
Liao
0.83 ( 0.56, 1.23)
Sakai
0.46 ( 0.32, 0.66)
Kim
1.48 ( 0.77, 2.82)
Sander
0.92 ( 0.62, 1.36)
Mazzanti
0.99 ( 0.75, 1.31)
Kotler
0.69 ( 0.36, 1.32)
Nolan
0.59 ( 0.28, 1.25)
Matsushita
0.65 ( 0.35, 1.20)
Stoltenberg
0.89 ( 0.33, 2.42)
Retz
0.56 ( 0.35, 0.88)
Gerra
0.51 ( 0.29, 0.89)
May
2.51 ( 0.85, 7.42)
Parsian
1.35 ( 0.81, 2.25)
Subtotal
0.84 ( 0.67, 1.05)
agegroup==3
Sweet
1.65 ( 1.19, 2.30)
Ha
0.59 ( 0.26, 1.36)
Pritchard
1.16 ( 0.78, 1.72)
Subtotal
1.18 ( 0.75, 1.87)
Overall
0.90 ( 0.74, 1.09)
.134688
1
7.42452
Odds ratio
31
3. By sample characteristics
Odds ratio
(95% CI)
Study
Forensic
Liao
0.83 ( 0.56, 1.23)
Mazzanti
0.99 ( 0.75, 1.31)
Retz
0.56 ( 0.35, 0.88)
Subtotal
0.80 ( 0.58, 1.10)
General
Beitchman
0.79 ( 0.58, 1.09)
Cao
1.28 ( 0.59, 2.78)
Sakai
0.46 ( 0.32, 0.66)
Subtotal
0.72 ( 0.44, 1.19)
Psychiatric
Kim
1.48 ( 0.77, 2.82)
Kotler
0.69 ( 0.36, 1.32)
Nolan
0.59 ( 0.28, 1.25)
May
2.51 ( 0.85, 7.42)
Sweet
1.65 ( 1.19, 2.30)
Ha
0.59 ( 0.26, 1.36)
Pritchard
1.16 ( 0.78, 1.72)
Subtotal
1.09 ( 0.77, 1.56)
Substance
Ishiguro
1.48 ( 0.84, 2.63)
Sander
0.92 ( 0.62, 1.36)
Matsushita
0.65 ( 0.35, 1.20)
Stoltenberg
0.89 ( 0.33, 2.42)
Gerra
0.51 ( 0.29, 0.89)
Parsian
1.35 ( 0.81, 2.25)
Subtotal
0.91 ( 0.65, 1.28)
Overall
0.90 ( 0.74, 1.09)
.134688
1
7.42452
Odds ratio
4. By outcome measure
Odds ratio
(95% CI)
Study
Aggresiveness
Beitchman
0.79 ( 0.58, 1.09)
Cao
1.28 ( 0.59, 2.78)
Sakai
0.46 ( 0.32, 0.66)
May
2.51 ( 0.85, 7.42)
Sweet
1.65 ( 1.19, 2.30)
Ha
0.59 ( 0.26, 1.36)
Pritchard
1.16 ( 0.78, 1.72)
Ishiguro
1.48 ( 0.84, 2.63)
Sander
0.92 ( 0.62, 1.36)
Stoltenberg
0.89 ( 0.33, 2.42)
Parsian
1.35 ( 0.81, 2.25)
Subtotal
1.04 ( 0.78, 1.39)
Offence
Liao
0.83 ( 0.56, 1.23)
Mazzanti
0.99 ( 0.75, 1.31)
Kotler
0.69 ( 0.36, 1.32)
Gerra
0.51 ( 0.29, 0.89)
Subtotal
0.79 ( 0.60, 1.05)
Violence
Retz
0.56 ( 0.35, 0.88)
Kim
1.48 ( 0.77, 2.82)
Nolan
0.59 ( 0.28, 1.25)
Matsushita
0.65 ( 0.35, 1.20)
Subtotal
0.73 ( 0.47, 1.14)
Overall
0.90 ( 0.74, 1.09)
.134688
1
7.42452
Odds ratio
32
5HTT-VNTR
Odds ratio
Study
(95% CI)
Beitchman
1.16 ( 0.72, 1.85)
May
0.87 ( 0.32, 2.41)
Pritchard
1.26 ( 0.85, 1.86)
Overall
1.18 ( 0.88, 1.58)
.316558
1
3.15897
Odds ratio
BDNF (val/met)
2. By Age (1: <16, 2: 16-65, 3: >65)
Odds ratio
(95% CI)
Study
agegroup==1
Guerin
1.13 ( 0.65, 1.96)
Subtotal
1.13 ( 0.65, 1.96)
agegroup==2
Tsai
0.95 ( 0.68, 1.32)
Chung
0.95 ( 0.54, 1.69)
Matsushita
0.60 ( 0.40, 0.89)
Subtotal
0.80 ( 0.58, 1.11)
Overall
0.86 ( 0.65, 1.13)
.399737
1
Odds ratio
33
2.50164
COMT
1. By ethnicity (1: caucasian, 0: other)
Odds ratio
(95% CI)
Study
0
Cao
Koen
Hong
Gu
Koh
Strous
Liou
Kweon
Subtotal
0.61 ( 0.28, 1.30)
1.03 ( 0.50, 2.12)
0.65 ( 0.39, 1.09)
1.11 ( 0.86, 1.43)
0.96 ( 0.63, 1.47)
0.42 ( 0.16, 1.06)
1.24 ( 0.76, 2.03)
0.42 ( 0.22, 0.81)
0.82 ( 0.63, 1.08)
1
Isir
Strous
Strous
Zammit
Hallikainen
Caspi
Grigorenko
Kotler
Caspi
Lachman
Tosato
Subtotal
1.06 ( 0.54, 2.10)
0.29 ( 0.15, 0.54)
0.40 ( 0.14, 1.20)
1.23 ( 0.89, 1.70)
1.09 ( 0.74, 1.61)
1.03 ( 0.79, 1.34)
1.28 ( 0.87, 1.89)
0.58 ( 0.31, 1.09)
2.36 ( 1.03, 5.39)
0.38 ( 0.18, 0.82)
0.65 ( 0.27, 1.55)
0.84 ( 0.63, 1.14)
Overall
0.84 ( 0.69, 1.02)
.136984
1
Odds ratio
7.30008
2. By Age (1: <16, 2: 16-65, 3: >65)
Study
Odds ratio
(95% CI)
agegroup==1
Cao
Isir
Subtotal
0.61 ( 0.28, 1.30)
1.06 ( 0.54, 2.10)
0.83 ( 0.48, 1.42)
agegroup==2
Koen
Hong
Gu
Koh
Strous
Liou
Kweon
Strous
Strous
Zammit
Hallikainen
Caspi
Grigorenko
Kotler
Caspi
Lachman
Tosato
Subtotal
1.03 ( 0.50, 2.12)
0.65 ( 0.39, 1.09)
1.11 ( 0.86, 1.43)
0.96 ( 0.63, 1.47)
0.42 ( 0.16, 1.06)
1.24 ( 0.76, 2.03)
0.42 ( 0.22, 0.81)
0.29 ( 0.15, 0.54)
0.40 ( 0.14, 1.20)
1.23 ( 0.89, 1.70)
1.09 ( 0.74, 1.61)
1.03 ( 0.79, 1.34)
1.28 ( 0.87, 1.89)
0.58 ( 0.31, 1.09)
2.36 ( 1.03, 5.39)
0.38 ( 0.18, 0.82)
0.65 ( 0.27, 1.55)
0.84 ( 0.68, 1.03)
Overall
0.84 ( 0.69, 1.02)
.136984
1
Odds ratio
7.30008
34
3. By sample characteristics
Odds ratio
(95% CI)
Study
Forensic
Isir
1.06 ( 0.54, 2.10)
Hallikainen
1.09 ( 0.74, 1.61)
Subtotal
1.08 ( 0.77, 1.52)
General
Cao
0.61 ( 0.28, 1.30)
Caspi
1.03 ( 0.79, 1.34)
Grigorenko
1.28 ( 0.87, 1.89)
Subtotal
1.04 ( 0.78, 1.38)
Psychiatric
Koen
1.03 ( 0.50, 2.12)
Hong
0.65 ( 0.39, 1.09)
Gu
1.11 ( 0.86, 1.43)
Koh
0.96 ( 0.63, 1.47)
Strous
0.42 ( 0.16, 1.06)
Liou
1.24 ( 0.76, 2.03)
Strous
0.29 ( 0.15, 0.54)
Strous
0.40 ( 0.14, 1.20)
Zammit
1.23 ( 0.89, 1.70)
Kotler
0.58 ( 0.31, 1.09)
Caspi
2.36 ( 1.03, 5.39)
Lachman
0.38 ( 0.18, 0.82)
Tosato
0.65 ( 0.27, 1.55)
Subtotal
0.78 ( 0.59, 1.04)
Substance
Kweon
0.42 ( 0.22, 0.81)
Subtotal
0.42 ( 0.22, 0.81)
Overall
0.84 ( 0.69, 1.02)
.136984
1
7.30008
Odds ratio
4. By outcome measure
Odds ratio
(95% CI)
Study
Aggresiveness
Koen
1.03 ( 0.50, 2.12)
Strous
0.29 ( 0.15, 0.54)
Strous
0.40 ( 0.14, 1.20)
Zammit
1.23 ( 0.89, 1.70)
Subtotal
0.65 ( 0.30, 1.42)
Offence
Isir
1.06 ( 0.54, 2.10)
Hallikainen
1.09 ( 0.74, 1.61)
Caspi
1.03 ( 0.79, 1.34)
Grigorenko
1.28 ( 0.87, 1.89)
Hong
0.65 ( 0.39, 1.09)
Gu
1.11 ( 0.86, 1.43)
Koh
0.96 ( 0.63, 1.47)
Kotler
0.58 ( 0.31, 1.09)
Caspi
2.36 ( 1.03, 5.39)
Subtotal
1.03 ( 0.87, 1.22)
Violence
Cao
0.61 ( 0.28, 1.30)
Strous
0.42 ( 0.16, 1.06)
Liou
1.24 ( 0.76, 2.03)
Lachman
0.38 ( 0.18, 0.82)
Tosato
0.65 ( 0.27, 1.55)
Kweon
0.42 ( 0.22, 0.81)
Subtotal
0.59 ( 0.38, 0.92)
Overall
0.84 ( 0.69, 1.02)
.136984
1
7.30008
Odds ratio
35
DAT1_gen
Odds ratio
Study
(95% CI)
Schulz-Heik
1.15 ( 0.71, 1.85)
Reif
1.33 ( 0.73, 2.43)
Caspi
1.17 ( 0.80, 1.72)
Overall
1.19 ( 0.91, 1.56)
.410900
1
2.43368
Odds ratio
DRD4_gen
2. By Age (1: <16, 2: 16-65, 3: >65)
Odds ratio
(95% CI)
Study
agegroup==1
Zai
1.53 ( 0.88, 2.64)
Subtotal
1.53 ( 0.88, 2.64)
agegroup==2
Fresan
3.47 ( 1.29, 9.33)
Caspi
0.96 ( 0.65, 1.41)
Kotler
1.19 ( 0.47, 3.04)
Subtotal
1.43 ( 0.69, 2.98)
Overall
1.40 ( 0.87, 2.26)
.107187
1
Odds ratio
36
9.32944
37
MAO-F
1. By ethnicity (1: caucasian, 0: other)
Odds ratio
(95% CI)
Study
0
Fresan
1.52 ( 0.42, 5.47)
Ducci
0.67 ( 0.41, 1.12)
Beaver
0.99 ( 0.40, 2.43)
Subtotal
0.80 ( 0.53, 1.22)
1
Strous
0.93 ( 0.33, 2.67)
Zammit
2.09 ( 0.76, 5.73)
Subtotal
1.42 ( 0.64, 3.12)
Overall
0.96 ( 0.64, 1.45)
.174620
1
Odds ratio
5.72668
3. By sample characteristics
Odds ratio
(95% CI)
Study
General
Beaver
0.99 ( 0.40, 2.43)
Subtotal
0.99 ( 0.40, 2.43)
Psychiatric
Fresan
1.52 ( 0.42, 5.47)
Strous
0.93 ( 0.33, 2.67)
Zammit
2.09 ( 0.76, 5.73)
Subtotal
1.44 ( 0.77, 2.72)
Substance
Ducci
0.67 ( 0.41, 1.12)
Subtotal
0.67 ( 0.41, 1.12)
Overall
0.96 ( 0.64, 1.45)
.174620
1
Odds ratio
38
5.72668
4. By outcome measure
Odds ratio
(95% CI)
Study
Aggresiveness
Fresan
1.52 ( 0.42, 5.47)
Strous
0.93 ( 0.33, 2.67)
Zammit
2.09 ( 0.76, 5.73)
Ducci
0.67 ( 0.41, 1.12)
Subtotal
1.03 ( 0.59, 1.79)
Violence
Beaver
0.99 ( 0.40, 2.43)
Subtotal
0.99 ( 0.40, 2.43)
Overall
0.96 ( 0.64, 1.45)
.174620
1
Odds ratio
39
5.72668
MAO-M
1. By ethnicity (1: caucasian, 0: other)
Odds ratio
(95% CI)
Study
0
Lu
Koen
Fresan
Beaver
Subtotal
0.79 ( 0.43, 1.46)
0.56 ( 0.20, 1.58)
2.31 ( 0.71, 7.45)
0.55 ( 0.31, 0.99)
0.77 ( 0.46, 1.27)
1
Samochowiec
Nolan
Caspi
Saito
Strous
Koller
Gerra
Foley
Zammit
Reif
Huizinga
Tikkanen
May
Subtotal
0.55 ( 0.31, 0.97)
0.51 ( 0.17, 1.57)
0.78 ( 0.42, 1.46)
0.97 ( 0.51, 1.82)
0.57 ( 0.23, 1.41)
1.12 ( 0.58, 2.15)
0.31 ( 0.12, 0.77)
1.54 ( 0.81, 2.94)
1.54 ( 0.69, 3.40)
0.53 ( 0.28, 0.98)
1.44 ( 0.77, 2.67)
1.56 ( 0.84, 2.90)
0.33 ( 0.11, 0.97)
0.83 ( 0.62, 1.12)
Overall
0.82 ( 0.64, 1.06)
.114913
1
Odds ratio
8.70218
2. By Age (1: <16, 2: 16-65, 3: >65)
Study
Odds ratio
(95% CI)
agegroup==1
Foley
Subtotal
1.54 ( 0.81, 2.94)
1.54 ( 0.81, 2.94)
agegroup==2
Lu
Koen
Fresan
Beaver
Samochowiec
Nolan
Caspi
Saito
Strous
Koller
Gerra
Zammit
Reif
Huizinga
Tikkanen
May
Subtotal
0.79 ( 0.43, 1.46)
0.56 ( 0.20, 1.58)
2.31 ( 0.71, 7.45)
0.55 ( 0.31, 0.99)
0.55 ( 0.31, 0.97)
0.51 ( 0.17, 1.57)
0.78 ( 0.42, 1.46)
0.97 ( 0.51, 1.82)
0.57 ( 0.23, 1.41)
1.12 ( 0.58, 2.15)
0.31 ( 0.12, 0.77)
1.54 ( 0.69, 3.40)
0.53 ( 0.28, 0.98)
1.44 ( 0.77, 2.67)
1.56 ( 0.84, 2.90)
0.33 ( 0.11, 0.97)
0.79 ( 0.61, 1.01)
Overall
0.82 ( 0.64, 1.06)
.114913
1
Odds ratio
8.70218
40
41
3. By sample characteristics
Odds ratio
(95% CI)
Study
Forensic
Lu
0.79 ( 0.43, 1.46)
Saito
0.97 ( 0.51, 1.82)
Reif
0.53 ( 0.28, 0.98)
Tikkanen
1.56 ( 0.84, 2.90)
Subtotal
0.89 ( 0.57, 1.39)
General
Foley
1.54 ( 0.81, 2.94)
Beaver
0.55 ( 0.31, 0.99)
Caspi
0.78 ( 0.42, 1.46)
Huizinga
1.44 ( 0.77, 2.67)
Subtotal
0.98 ( 0.60, 1.60)
Psychiatric
Koen
0.56 ( 0.20, 1.58)
Fresan
2.31 ( 0.71, 7.45)
Nolan
0.51 ( 0.17, 1.57)
Strous
0.57 ( 0.23, 1.41)
Zammit
1.54 ( 0.69, 3.40)
May
0.33 ( 0.11, 0.97)
Subtotal
0.77 ( 0.43, 1.37)
Substance
Samochowiec
0.55 ( 0.31, 0.97)
Koller
1.12 ( 0.58, 2.15)
Gerra
0.31 ( 0.12, 0.77)
Subtotal
0.60 ( 0.31, 1.18)
Overall
0.82 ( 0.64, 1.06)
.114913
1
8.70218
Odds ratio
4. By outcome measure
Odds ratio
(95% CI)
Study
Aggresiveness
Foley
1.54 ( 0.81, 2.94)
Huizinga
1.44 ( 0.77, 2.67)
Koen
0.56 ( 0.20, 1.58)
Fresan
2.31 ( 0.71, 7.45)
Strous
0.57 ( 0.23, 1.41)
Zammit
1.54 ( 0.69, 3.40)
May
0.33 ( 0.11, 0.97)
Samochowiec
0.55 ( 0.31, 0.97)
Koller
1.12 ( 0.58, 2.15)
Subtotal
0.95 ( 0.65, 1.40)
Offence
Lu
0.79 ( 0.43, 1.46)
Saito
0.97 ( 0.51, 1.82)
Reif
0.53 ( 0.28, 0.98)
Tikkanen
1.56 ( 0.84, 2.90)
Gerra
0.31 ( 0.12, 0.77)
Subtotal
0.76 ( 0.46, 1.24)
Violence
Beaver
0.55 ( 0.31, 0.99)
Caspi
0.78 ( 0.42, 1.46)
Nolan
0.51 ( 0.17, 1.57)
Subtotal
0.63 ( 0.42, 0.94)
Overall
0.82 ( 0.64, 1.06)
.114913
1
8.70218
Odds ratio
42
TPH
1. By ethnicity (1: caucasian, 0: other)
Odds ratio
(95% CI)
Study
0
Kim
1.05 ( 0.67, 1.65)
Koh
1.36 ( 0.94, 1.98)
Subtotal
1.23 ( 0.92, 1.63)
1
Nielsen
0.88 ( 0.69, 1.13)
Nolan
2.47 ( 1.14, 5.35)
Craig
1.27 ( 0.96, 1.70)
Subtotal
1.24 ( 0.81, 1.90)
Overall
1.19 ( 0.92, 1.55)
.186974
1
Odds ratio
5.34832
2. By Age (1: <16, 2: 16-65, 3: >65)
Odds ratio
(95% CI)
Study
agegroup==2
Kim
1.05 ( 0.67, 1.65)
Koh
1.36 ( 0.94, 1.98)
Nielsen
0.88 ( 0.69, 1.13)
Nolan
2.47 ( 1.14, 5.35)
Subtotal
1.20 ( 0.85, 1.69)
agegroup==3
Craig
1.27 ( 0.96, 1.70)
Subtotal
1.27 ( 0.96, 1.70)
Overall
1.19 ( 0.92, 1.55)
.186974
1
Odds ratio
43
5.34832
3. By sample characteristics
Odds ratio
(95% CI)
Study
Forensic
Nielsen
0.88 ( 0.69, 1.13)
Subtotal
0.88 ( 0.69, 1.13)
Psychiatric
Kim
1.05 ( 0.67, 1.65)
Koh
1.36 ( 0.94, 1.98)
Nolan
2.47 ( 1.14, 5.35)
Craig
1.27 ( 0.96, 1.70)
Subtotal
1.31 ( 1.05, 1.64)
Overall
1.19 ( 0.92, 1.55)
.186974
1
Odds ratio
44
5.34832
AR (CAG)
Odds ratio
Study
(95% CI)
Cheng
4.32 ( 0.94, 19.90)
Rajender
5.64 ( 4.00, 7.96)
Aluja
1.28 ( 0.76, 2.14)
Overall
3.04 ( 0.94, 9.84)
.050243
1
19.9029
Odds ratio
DRD2
Odds ratio
Study
(95% CI)
Zai
1.66 ( 1.11, 2.50)
Kasiakogia
1.14 ( 0.91, 1.42)
Goldman
1.56 ( 0.45, 5.43)
Overall
1.30 ( 0.99, 1.71)
.184092
1
5.43205
Odds ratio
45
Supplementary Figure 2. Forest Plots of meta-analyses of studies with continuous outcomes
5HT-2A A1438G Dominant
Effect size
Study
(95% CI)
Preuss
-0.54 (-0.93,-0.14)
Perroud
-0.15 (-0.33, 0.04)
Giegling
-0.08 (-0.28, 0.13)
Overall
-0.19 (-0.39, 0.01)
-2.2221
0
2.22214
Effect size
5HT-2A A1438G Recessive
Effect size
Study
(95% CI)
Preuss
-0.14 (-0.55, 0.27)
Perroud
0.01 (-0.18, 0.20)
Giegling
0.31 ( 0.05, 0.56)
Overall
0.08 (-0.15, 0.32)
-2.7171
0
2.71712
Effect size
46
5HT-2A A1438G Additive
Effect size
Study
(95% CI)
Preuss
0.68 ( 0.04, 1.33)
Perroud
0.32 (-0.37, 1.02)
Giegling
-0.19 (-0.67, 0.30)
Overall
0.24 (-0.30, 0.77)
-12.283
0
12.2831
Effect size
47
5HTTLPR Dominant
1. By ethnicity (1: caucasian, 0: other)
Effect size
(95% CI)
Study
caucasian==0
Greenberg
-0.07 (-0.24, 0.10)
Patkar
-0.08 (-0.61, 0.45)
Han
-0.11 (-0.42, 0.21)
Verona
-0.14 (-0.52, 0.24)
Silva
0.17 (-0.42, 0.76)
Terraciano
-0.08 (-0.30, 0.14)
Kim
-0.43 (-1.02, 0.16)
Kim
-0.56 (-1.13, 0.01)
Yang
0.00 (-0.33, 0.34)
Subtotal
-0.09 (-0.20, 0.01)
caucasian==1
Zalsman
0.08 (-0.53, 0.68)
Twitchell
0.64 ( 0.01, 1.26)
Gerra
-0.46 (-0.89,-0.03)
Gerra
-0.31 (-0.85, 0.23)
Gerra
-0.60 (-0.96,-0.24)
Baca-Garcia
-0.82 (-1.51,-0.13)
Baca-Garcia
0.01 (-0.35, 0.37)
Baca-Garcia
-0.21 (-0.73, 0.31)
Baca-Garcia
0.28 (-0.31, 0.88)
Gonda
0.15 (-0.29, 0.58)
Sysoeva
1.35 ( 0.48, 2.22)
Sysoeva
-0.73 (-1.52, 0.06)
Sysoeva
-0.20 (-0.91, 0.51)
Terraciano
-0.03 (-0.11, 0.04)
Perroud
0.13 (-0.03, 0.29)
Pombo
-0.08 (-0.58, 0.42)
Hohmann
-0.04 (-0.37, 0.28)
Subtotal
-0.07 (-0.22, 0.08)
Overall
-0.08 (-0.18, 0.02)
-2.2221
0
2.22214
Effect size
2. By Age (1: <16, 2: 16-65, 3: >65)
Effect size
(95% CI)
Study
agegroup==1
Twitchell
0.64 ( 0.01, 1.26)
Sysoeva
1.35 ( 0.48, 2.22)
Sysoeva
-0.20 (-0.91, 0.51)
Hohmann
-0.04 (-0.37, 0.28)
Subtotal
0.37 (-0.23, 0.96)
agegroup==2
Greenberg
-0.07 (-0.24, 0.10)
Patkar
-0.08 (-0.61, 0.45)
Han
-0.11 (-0.42, 0.21)
Verona
-0.14 (-0.52, 0.24)
Silva
0.17 (-0.42, 0.76)
Terraciano
-0.08 (-0.30, 0.14)
Kim
-0.43 (-1.02, 0.16)
Kim
-0.56 (-1.13, 0.01)
Yang
0.00 (-0.33, 0.34)
Zalsman
0.08 (-0.53, 0.68)
Gerra
-0.46 (-0.89,-0.03)
Gerra
-0.31 (-0.85, 0.23)
Gerra
-0.60 (-0.96,-0.24)
Baca-Garcia
-0.82 (-1.51,-0.13)
Baca-Garcia
0.01 (-0.35, 0.37)
Baca-Garcia
-0.21 (-0.73, 0.31)
Baca-Garcia
0.28 (-0.31, 0.88)
Gonda
0.15 (-0.29, 0.58)
Sysoeva
-0.73 (-1.52, 0.06)
Terraciano
-0.03 (-0.11, 0.04)
Perroud
0.13 (-0.03, 0.29)
Pombo
-0.08 (-0.58, 0.42)
Subtotal
-0.11 (-0.20,-0.01)
Overall
-0.08 (-0.18, 0.02)
-2.2221
0
2.22214
Effect size
48
49
3. By sample characteristics
Effect size
(95% CI)
Study
General
Twitchell
0.64 ( 0.01, 1.26)
Sysoeva
1.35 ( 0.48, 2.22)
Sysoeva
-0.20 (-0.91, 0.51)
Hohmann
-0.04 (-0.37, 0.28)
Greenberg
-0.07 (-0.24, 0.10)
Verona
-0.14 (-0.52, 0.24)
Terraciano
-0.08 (-0.30, 0.14)
Yang
0.00 (-0.33, 0.34)
Gerra
-0.31 (-0.85, 0.23)
Baca-Garcia
-0.21 (-0.73, 0.31)
Baca-Garcia
0.28 (-0.31, 0.88)
Gonda
0.15 (-0.29, 0.58)
Sysoeva
-0.73 (-1.52, 0.06)
Terraciano
-0.03 (-0.11, 0.04)
Subtotal
-0.02 (-0.14, 0.09)
Psychiatric
Han
-0.11 (-0.42, 0.21)
Silva
0.17 (-0.42, 0.76)
Kim
-0.43 (-1.02, 0.16)
Kim
-0.56 (-1.13, 0.01)
Zalsman
0.08 (-0.53, 0.68)
Baca-Garcia
-0.82 (-1.51,-0.13)
Baca-Garcia
0.01 (-0.35, 0.37)
Perroud
0.13 (-0.03, 0.29)
Subtotal
-0.11 (-0.33, 0.10)
Substance
Patkar
-0.08 (-0.61, 0.45)
Gerra
-0.46 (-0.89,-0.03)
Gerra
-0.60 (-0.96,-0.24)
Pombo
-0.08 (-0.58, 0.42)
Subtotal
-0.35 (-0.62,-0.09)
Overall
-0.08 (-0.18, 0.02)
-2.2221
0
2.22214
Effect size
4. By outcome measure
Effect size
(95% CI)
Study
Aggressiveness
Twitchell
0.64 ( 0.01, 1.26)
Sysoeva
1.35 ( 0.48, 2.22)
Sysoeva
-0.20 (-0.91, 0.51)
Hohmann
-0.04 (-0.37, 0.28)
Verona
-0.14 (-0.52, 0.24)
Gerra
-0.31 (-0.85, 0.23)
Baca-Garcia
-0.21 (-0.73, 0.31)
Baca-Garcia
0.28 (-0.31, 0.88)
Gonda
0.15 (-0.29, 0.58)
Sysoeva
-0.73 (-1.52, 0.06)
Han
-0.11 (-0.42, 0.21)
Silva
0.17 (-0.42, 0.76)
Zalsman
0.08 (-0.53, 0.68)
Baca-Garcia
-0.82 (-1.51,-0.13)
Baca-Garcia
0.01 (-0.35, 0.37)
Patkar
-0.08 (-0.61, 0.45)
Gerra
-0.46 (-0.89,-0.03)
Gerra
-0.60 (-0.96,-0.24)
Pombo
-0.08 (-0.58, 0.42)
Subtotal
-0.09 (-0.26, 0.07)
Anger
Greenberg
-0.07 (-0.24, 0.10)
Terraciano
-0.08 (-0.30, 0.14)
Yang
0.00 (-0.33, 0.34)
Terraciano
-0.03 (-0.11, 0.04)
Kim
-0.43 (-1.02, 0.16)
Kim
-0.56 (-1.13, 0.01)
Perroud
0.13 (-0.03, 0.29)
Subtotal
-0.04 (-0.13, 0.06)
Overall
-0.08 (-0.18, 0.02)
-2.2221
0
2.22214
Effect size
50
5HTTLPR Recessive
1. By ethnicity (1: caucasian, 0: other)
Effect size
(95% CI)
Study
caucasian==0
Greenberg
-0.32 (-0.46,-0.18)
Patkar
0.01 (-0.38, 0.41)
Han
-0.23 (-0.99, 0.53)
Verona
-0.12 (-0.84, 0.60)
Silva
-0.06 (-0.78, 0.66)
Terraciano
0.03 (-0.15, 0.20)
Kim
-1.29 (-2.49,-0.09)
Kim
-0.64 (-1.57, 0.28)
Yang
0.39 (-0.29, 1.07)
Subtotal
-0.14 (-0.35, 0.07)
caucasian==1
Zalsman
1.05 ( 0.26, 1.84)
Twitchell
0.70 ( 0.12, 1.28)
Gerra
-0.21 (-0.65, 0.23)
Gerra
-0.33 (-0.75, 0.08)
Gerra
-0.53 (-0.81,-0.24)
Nobile
-0.07 (-0.24, 0.10)
Baca-Garcia
-0.08 (-0.60, 0.44)
Baca-Garcia
0.35 (-0.07, 0.78)
Baca-Garcia
0.27 (-0.20, 0.75)
Baca-Garcia
-0.28 (-0.75, 0.19)
Gonda
-0.16 (-0.48, 0.15)
Sysoeva
-0.14 (-0.67, 0.39)
Sysoeva
-0.05 (-0.70, 0.60)
Sysoeva
0.23 (-0.27, 0.73)
Terraciano
-0.04 (-0.11, 0.03)
Perroud
0.04 (-0.12, 0.19)
May
0.87 ( 0.14, 1.61)
Pombo
-0.12 (-0.55, 0.31)
Hohmann
0.03 (-0.21, 0.27)
Zimmerman
-0.42 (-0.84, 0.01)
Gonda
0.38 ( 0.03, 0.74)
Gonda
-0.37 (-0.75,-0.00)
Subtotal
-0.02 (-0.13, 0.09)
Overall
-0.05 (-0.14, 0.05)
-2.4941
0
2.49415
Effect size
2. By Age (1: <16, 2: 16-65, 3: >65)
Effect size
(95% CI)
Study
agegroup==1
Twitchell
0.70 ( 0.12, 1.28)
Nobile
-0.07 (-0.24, 0.10)
Sysoeva
-0.14 (-0.67, 0.39)
Sysoeva
0.23 (-0.27, 0.73)
Hohmann
0.03 (-0.21, 0.27)
Zimmerman
-0.42 (-0.84, 0.01)
Subtotal
0.01 (-0.21, 0.22)
agegroup==2
Greenberg
-0.32 (-0.46,-0.18)
Patkar
0.01 (-0.38, 0.41)
Han
-0.23 (-0.99, 0.53)
Verona
-0.12 (-0.84, 0.60)
Silva
-0.06 (-0.78, 0.66)
Terraciano
0.03 (-0.15, 0.20)
Kim
-1.29 (-2.49,-0.09)
Kim
-0.64 (-1.57, 0.28)
Yang
0.39 (-0.29, 1.07)
Zalsman
1.05 ( 0.26, 1.84)
Gerra
-0.21 (-0.65, 0.23)
Gerra
-0.33 (-0.75, 0.08)
Gerra
-0.53 (-0.81,-0.24)
Baca-Garcia
-0.08 (-0.60, 0.44)
Baca-Garcia
0.35 (-0.07, 0.78)
Baca-Garcia
0.27 (-0.20, 0.75)
Baca-Garcia
-0.28 (-0.75, 0.19)
Gonda
-0.16 (-0.48, 0.15)
Sysoeva
-0.05 (-0.70, 0.60)
Terraciano
-0.04 (-0.11, 0.03)
Perroud
0.04 (-0.12, 0.19)
May
0.87 ( 0.14, 1.61)
Pombo
-0.12 (-0.55, 0.31)
Gonda
0.38 ( 0.03, 0.74)
Gonda
-0.37 (-0.75,-0.00)
Subtotal
-0.06 (-0.17, 0.05)
Overall
-0.05 (-0.14, 0.05)
-2.4941
0
2.49415
Effect size
51
3. By sample characteristics
Effect size
(95% CI)
Study
General
Twitchell
0.70 ( 0.12, 1.28)
Nobile
-0.07 (-0.24, 0.10)
Sysoeva
-0.14 (-0.67, 0.39)
Sysoeva
0.23 (-0.27, 0.73)
Hohmann
0.03 (-0.21, 0.27)
Zimmerman
-0.42 (-0.84, 0.01)
Greenberg
-0.32 (-0.46,-0.18)
Verona
-0.12 (-0.84, 0.60)
Terraciano
0.03 (-0.15, 0.20)
Yang
0.39 (-0.29, 1.07)
Gerra
-0.33 (-0.75, 0.08)
Baca-Garcia
0.27 (-0.20, 0.75)
Baca-Garcia
-0.28 (-0.75, 0.19)
Gonda
-0.16 (-0.48, 0.15)
Sysoeva
-0.05 (-0.70, 0.60)
Terraciano
-0.04 (-0.11, 0.03)
Gonda
-0.37 (-0.75,-0.00)
Subtotal
-0.08 (-0.19, 0.02)
Psychiatric
Han
-0.23 (-0.99, 0.53)
Silva
-0.06 (-0.78, 0.66)
Kim
-1.29 (-2.49,-0.09)
Kim
-0.64 (-1.57, 0.28)
Zalsman
1.05 ( 0.26, 1.84)
Baca-Garcia
-0.08 (-0.60, 0.44)
Baca-Garcia
0.35 (-0.07, 0.78)
Perroud
0.04 (-0.12, 0.19)
May
0.87 ( 0.14, 1.61)
Gonda
0.38 ( 0.03, 0.74)
Subtotal
0.14 (-0.13, 0.40)
Substance
Patkar
0.01 (-0.38, 0.41)
Gerra
-0.21 (-0.65, 0.23)
Gerra
-0.53 (-0.81,-0.24)
Pombo
-0.12 (-0.55, 0.31)
Subtotal
-0.24 (-0.50, 0.02)
Overall
-0.05 (-0.14, 0.05)
-2.4941
0
2.49415
Effect size
4. By outcome measure
Effect size
(95% CI)
Study
Aggressiveness
Twitchell
0.70 ( 0.12, 1.28)
Nobile
-0.07 (-0.24, 0.10)
Sysoeva
-0.14 (-0.67, 0.39)
Sysoeva
0.23 (-0.27, 0.73)
Hohmann
0.03 (-0.21, 0.27)
Zimmerman
-0.42 (-0.84, 0.01)
Verona
-0.12 (-0.84, 0.60)
Gerra
-0.33 (-0.75, 0.08)
Baca-Garcia
0.27 (-0.20, 0.75)
Baca-Garcia
-0.28 (-0.75, 0.19)
Gonda
-0.16 (-0.48, 0.15)
Sysoeva
-0.05 (-0.70, 0.60)
Gonda
-0.37 (-0.75,-0.00)
Han
-0.23 (-0.99, 0.53)
Silva
-0.06 (-0.78, 0.66)
Zalsman
1.05 ( 0.26, 1.84)
Baca-Garcia
-0.08 (-0.60, 0.44)
Baca-Garcia
0.35 (-0.07, 0.78)
May
0.87 ( 0.14, 1.61)
Gonda
0.38 ( 0.03, 0.74)
Patkar
0.01 (-0.38, 0.41)
Gerra
-0.21 (-0.65, 0.23)
Gerra
-0.53 (-0.81,-0.24)
Pombo
-0.12 (-0.55, 0.31)
Subtotal
-0.02 (-0.15, 0.11)
Anger
Greenberg
-0.32 (-0.46,-0.18)
Terraciano
0.03 (-0.15, 0.20)
Yang
0.39 (-0.29, 1.07)
Terraciano
-0.04 (-0.11, 0.03)
Kim
-1.29 (-2.49,-0.09)
Kim
-0.64 (-1.57, 0.28)
Perroud
0.04 (-0.12, 0.19)
Subtotal
-0.09 (-0.24, 0.07)
Overall
-0.05 (-0.14, 0.05)
-2.4941
0
2.49415
Effect size
52
5HTTLPR Additive
1. By ethnicity (1: caucasian, 0: other)
Effect size
(95% CI)
Study
caucasian==0
Verona
0.76 (-1.33, 2.85)
Han
0.59 (-0.93, 2.11)
Silva
-0.94 (-7.53, 5.64)
Patkar
0.07 (-1.31, 1.45)
Greenberg
1.92 ( 0.81, 3.03)
Terraciano
0.09 (-0.91, 1.10)
Yang
-0.43 (-2.18, 1.33)
Kim
2.58 (-0.00, 5.16)
Kim
1.90 ( 0.01, 3.78)
Subtotal
0.79 ( 0.11, 1.47)
caucasian==1
Twitchell
-3.21 (-5.53,-0.89)
Sysoeva
-0.42 (-1.22, 0.37)
Sysoeva
-0.42 (-1.22, 0.37)
Hohmann
-0.01 (-0.84, 0.81)
Gerra
2.10 (-0.34, 4.54)
Baca-Garcia
-0.06 (-0.48, 0.37)
Baca-Garcia
0.06 (-0.36, 0.48)
Gonda
0.05 (-0.23, 0.33)
Sysoeva
-0.42 (-1.22, 0.37)
Zalsman
-1.23 (-2.84, 0.37)
Baca-Garcia
1.63 (-0.65, 3.91)
Baca-Garcia
-0.48 (-1.49, 0.52)
Gerra
2.75 (-0.21, 5.72)
Gerra
3.76 ( 2.03, 5.49)
Pombo
0.42 (-1.19, 2.03)
Terraciano
0.25 (-0.16, 0.66)
Perroud
-0.37 (-0.94, 0.21)
Subtotal
-0.01 (-0.32, 0.31)
Overall
0.17 (-0.13, 0.47)
-7.5261
0
7.52614
Effect size
2. By Age (1: <16, 2: 16-65, 3: >65)
Effect size
(95% CI)
Study
agegroup==1
Twitchell
-3.21 (-5.53,-0.89)
Sysoeva
-0.42 (-1.22, 0.37)
Sysoeva
-0.42 (-1.22, 0.37)
Hohmann
-0.01 (-0.84, 0.81)
Subtotal
-0.52 (-1.25, 0.20)
agegroup==2
Verona
0.76 (-1.33, 2.85)
Han
0.59 (-0.93, 2.11)
Silva
-0.94 (-7.53, 5.64)
Patkar
0.07 (-1.31, 1.45)
Greenberg
1.92 ( 0.81, 3.03)
Terraciano
0.09 (-0.91, 1.10)
Yang
-0.43 (-2.18, 1.33)
Kim
2.58 (-0.00, 5.16)
Kim
1.90 ( 0.01, 3.78)
Gerra
2.10 (-0.34, 4.54)
Baca-Garcia
-0.06 (-0.48, 0.37)
Baca-Garcia
0.06 (-0.36, 0.48)
Gonda
0.05 (-0.23, 0.33)
Sysoeva
-0.42 (-1.22, 0.37)
Zalsman
-1.23 (-2.84, 0.37)
Baca-Garcia
1.63 (-0.65, 3.91)
Baca-Garcia
-0.48 (-1.49, 0.52)
Gerra
2.75 (-0.21, 5.72)
Gerra
3.76 ( 2.03, 5.49)
Pombo
0.42 (-1.19, 2.03)
Terraciano
0.25 (-0.16, 0.66)
Perroud
-0.37 (-0.94, 0.21)
Subtotal
0.32 (-0.01, 0.64)
Overall
0.17 (-0.13, 0.47)
-7.5261
0
7.52614
Effect size
53
3. By sample characteristics
Effect size
(95% CI)
Study
General
Twitchell
-3.21 (-5.53,-0.89)
Sysoeva
-0.42 (-1.22, 0.37)
Sysoeva
-0.42 (-1.22, 0.37)
Hohmann
-0.01 (-0.84, 0.81)
Verona
0.76 (-1.33, 2.85)
Greenberg
1.92 ( 0.81, 3.03)
Terraciano
0.09 (-0.91, 1.10)
Yang
-0.43 (-2.18, 1.33)
Gerra
2.10 (-0.34, 4.54)
Baca-Garcia
-0.06 (-0.48, 0.37)
Baca-Garcia
0.06 (-0.36, 0.48)
Gonda
0.05 (-0.23, 0.33)
Sysoeva
-0.42 (-1.22, 0.37)
Terraciano
0.25 (-0.16, 0.66)
Subtotal
0.03 (-0.25, 0.31)
Psychiatric
Han
0.59 (-0.93, 2.11)
Silva
-0.94 (-7.53, 5.64)
Kim
2.58 (-0.00, 5.16)
Kim
1.90 ( 0.01, 3.78)
Zalsman
-1.23 (-2.84, 0.37)
Baca-Garcia
1.63 (-0.65, 3.91)
Baca-Garcia
-0.48 (-1.49, 0.52)
Perroud
-0.37 (-0.94, 0.21)
Subtotal
0.25 (-0.54, 1.05)
Substance
Patkar
0.07 (-1.31, 1.45)
Gerra
2.75 (-0.21, 5.72)
Gerra
3.76 ( 2.03, 5.49)
Pombo
0.42 (-1.19, 2.03)
Subtotal
1.62 (-0.25, 3.49)
Overall
0.17 (-0.13, 0.47)
-7.5261
0
7.52614
Effect size
4. By outcome measure
Effect size
(95% CI)
Study
Aggressiveness
Twitchell
-3.21 (-5.53,-0.89)
Sysoeva
-0.42 (-1.22, 0.37)
Sysoeva
-0.42 (-1.22, 0.37)
Hohmann
-0.01 (-0.84, 0.81)
Verona
0.76 (-1.33, 2.85)
Gerra
2.10 (-0.34, 4.54)
Baca-Garcia
-0.06 (-0.48, 0.37)
Baca-Garcia
0.06 (-0.36, 0.48)
Gonda
0.05 (-0.23, 0.33)
Sysoeva
-0.42 (-1.22, 0.37)
Han
0.59 (-0.93, 2.11)
Silva
-0.94 (-7.53, 5.64)
Zalsman
-1.23 (-2.84, 0.37)
Baca-Garcia
1.63 (-0.65, 3.91)
Baca-Garcia
-0.48 (-1.49, 0.52)
Patkar
0.07 (-1.31, 1.45)
Gerra
2.75 (-0.21, 5.72)
Gerra
3.76 ( 2.03, 5.49)
Pombo
0.42 (-1.19, 2.03)
Subtotal
0.04 (-0.30, 0.39)
Anger
Greenberg
1.92 ( 0.81, 3.03)
Terraciano
0.09 (-0.91, 1.10)
Yang
-0.43 (-2.18, 1.33)
Terraciano
0.25 (-0.16, 0.66)
Kim
2.58 (-0.00, 5.16)
Kim
1.90 ( 0.01, 3.78)
Perroud
-0.37 (-0.94, 0.21)
Subtotal
0.55 (-0.13, 1.24)
Overall
0.17 (-0.13, 0.47)
-7.5261
0
7.52614
Effect size
54
BDNF
Effect size
Study
(95% CI)
Wagner
-0.17 (-0.49, 0.14)
Sen
0.05 (-0.14, 0.24)
Perroud
-0.02 (-0.16, 0.12)
Overall
-0.01 (-0.12, 0.09)
-2.7171
0
2.71712
Effect size
55
COMT Dominant
1. By ethnicity (1: caucasian, 0: other)
Effect size
(95% CI)
Study
caucasian==0
Han
-0.68 (-1.25,-0.11)
Han
-1.01 (-1.74,-0.29)
Kang
-0.11 (-0.60, 0.38)
Kang
0.05 (-0.55, 0.64)
Volavka
-0.96 (-1.76,-0.15)
Subtotal
-0.49 (-0.91,-0.07)
caucasian==1
Caspi
-0.00 (-0.10, 0.10)
Avramopoul
0.17 (-0.09, 0.43)
Caspi
0.13 (-0.16, 0.43)
Caspi
0.12 (-0.20, 0.45)
Strous
-0.82 (-1.32,-0.32)
Strous
-0.78 (-1.63, 0.06)
Zammit
-0.03 (-0.27, 0.22)
Flory
0.33 (-0.13, 0.79)
Caspi
0.44 (-0.24, 1.11)
Wagner
0.18 (-0.15, 0.52)
Nedic
-0.06 (-0.57, 0.46)
Nedic
0.16 (-0.15, 0.47)
Nedic
0.10 (-0.74, 0.94)
Nedic
0.20 (-0.39, 0.79)
Rujescu
-0.17 (-0.40, 0.05)
Perroud
0.17 (-0.00, 0.34)
Subtotal
0.04 (-0.06, 0.15)
Overall
-0.03 (-0.15, 0.09)
-1.7628
0
1.76282
Effect size
2. By Age (1: <16, 2: 16-65, 3: >65)
Effect size
(95% CI)
Study
agegroup==1
Caspi
-0.00 (-0.10, 0.10)
Caspi
0.13 (-0.16, 0.43)
Caspi
0.12 (-0.20, 0.45)
Subtotal
0.02 (-0.07, 0.12)
agegroup==2
Han
-0.68 (-1.25,-0.11)
Han
-1.01 (-1.74,-0.29)
Kang
-0.11 (-0.60, 0.38)
Kang
0.05 (-0.55, 0.64)
Volavka
-0.96 (-1.76,-0.15)
Avramopoul
0.17 (-0.09, 0.43)
Strous
-0.82 (-1.32,-0.32)
Strous
-0.78 (-1.63, 0.06)
Zammit
-0.03 (-0.27, 0.22)
Flory
0.33 (-0.13, 0.79)
Caspi
0.44 (-0.24, 1.11)
Wagner
0.18 (-0.15, 0.52)
Nedic
-0.06 (-0.57, 0.46)
Nedic
0.16 (-0.15, 0.47)
Nedic
0.10 (-0.74, 0.94)
Nedic
0.20 (-0.39, 0.79)
Rujescu
-0.17 (-0.40, 0.05)
Perroud
0.17 (-0.00, 0.34)
Subtotal
-0.08 (-0.24, 0.08)
Overall
-0.03 (-0.15, 0.09)
-1.7628
0
1.76282
Effect size
56
57
3. By sample characteristics
Effect size
(95% CI)
Study
General
Caspi
-0.00 (-0.10, 0.10)
Kang
-0.11 (-0.60, 0.38)
Kang
0.05 (-0.55, 0.64)
Avramopoul
0.17 (-0.09, 0.43)
Subtotal
0.02 (-0.07, 0.11)
Psychiatric
Caspi
0.13 (-0.16, 0.43)
Caspi
0.12 (-0.20, 0.45)
Han
-0.68 (-1.25,-0.11)
Han
-1.01 (-1.74,-0.29)
Volavka
-0.96 (-1.76,-0.15)
Strous
-0.82 (-1.32,-0.32)
Strous
-0.78 (-1.63, 0.06)
Zammit
-0.03 (-0.27, 0.22)
Flory
0.33 (-0.13, 0.79)
Caspi
0.44 (-0.24, 1.11)
Wagner
0.18 (-0.15, 0.52)
Rujescu
-0.17 (-0.40, 0.05)
Perroud
0.17 (-0.00, 0.34)
Subtotal
-0.13 (-0.33, 0.07)
Substance
Nedic
-0.06 (-0.57, 0.46)
Nedic
0.16 (-0.15, 0.47)
Nedic
0.10 (-0.74, 0.94)
Nedic
0.20 (-0.39, 0.79)
Subtotal
0.12 (-0.11, 0.35)
Overall
-0.03 (-0.15, 0.09)
-1.7628
0
1.76282
Effect size
4. By outcome measure
Effect size
(95% CI)
Study
Aggressiveness
Caspi
-0.00 (-0.10, 0.10)
Avramopoul
0.17 (-0.09, 0.43)
Caspi
0.13 (-0.16, 0.43)
Caspi
0.12 (-0.20, 0.45)
Han
-0.68 (-1.25,-0.11)
Han
-1.01 (-1.74,-0.29)
Strous
-0.82 (-1.32,-0.32)
Strous
-0.78 (-1.63, 0.06)
Zammit
-0.03 (-0.27, 0.22)
Flory
0.33 (-0.13, 0.79)
Caspi
0.44 (-0.24, 1.11)
Wagner
0.18 (-0.15, 0.52)
Nedic
-0.06 (-0.57, 0.46)
Nedic
0.16 (-0.15, 0.47)
Nedic
0.10 (-0.74, 0.94)
Nedic
0.20 (-0.39, 0.79)
Subtotal
-0.02 (-0.16, 0.13)
Anger
Kang
-0.11 (-0.60, 0.38)
Kang
0.05 (-0.55, 0.64)
Volavka
-0.96 (-1.76,-0.15)
Rujescu
-0.17 (-0.40, 0.05)
Perroud
0.17 (-0.00, 0.34)
Subtotal
-0.09 (-0.37, 0.18)
Overall
-0.03 (-0.15, 0.09)
-1.7628
0
1.76282
Effect size
58
COMT Recessive
1. By ethnicity (1: caucasian, 0: other)
Effect size
(95% CI)
Study
caucasian==0
Albaugh
-0.43 (-0.78,-0.08)
Sengupta
0.05 (-0.27, 0.38)
Han
-0.25 (-0.55, 0.06)
Han
-0.36 (-0.71,-0.00)
Kang
0.12 (-0.17, 0.41)
Kang
-0.02 (-0.38, 0.33)
Volavka
0.16 (-0.37, 0.69)
Subtotal
-0.11 (-0.29, 0.06)
caucasian==1
Caspi
-0.03 (-0.14, 0.07)
Avramopoul
0.16 (-0.08, 0.40)
Caspi
0.32 ( 0.01, 0.63)
Caspi
0.43 ( 0.09, 0.77)
Strous
-0.42 (-0.85,-0.00)
Strous
-0.70 (-1.62, 0.22)
Zammit
0.18 (-0.07, 0.42)
Flory
0.44 (-0.17, 1.05)
Caspi
0.78 ( 0.09, 1.47)
Wagner
-0.20 (-0.61, 0.22)
Nedic
0.21 (-0.63, 1.06)
Nedic
0.21 (-0.07, 0.50)
Nedic
1.43 ( 0.14, 2.72)
Nedic
0.39 (-0.21, 1.00)
Rujescu
0.10 (-0.14, 0.33)
Perroud
0.17 ( 0.02, 0.32)
Subtotal
0.14 ( 0.02, 0.27)
Overall
0.06 (-0.04, 0.17)
-2.7171
0
2.71712
Effect size
2. By Age (1: <16, 2: 16-65, 3: >65)
Effect size
(95% CI)
Study
agegroup==1
Albaugh
-0.43 (-0.78,-0.08)
Sengupta
0.05 (-0.27, 0.38)
Caspi
-0.03 (-0.14, 0.07)
Caspi
0.32 ( 0.01, 0.63)
Caspi
0.43 ( 0.09, 0.77)
Subtotal
0.06 (-0.18, 0.30)
agegroup==2
Han
-0.25 (-0.55, 0.06)
Han
-0.36 (-0.71,-0.00)
Kang
0.12 (-0.17, 0.41)
Kang
-0.02 (-0.38, 0.33)
Volavka
0.16 (-0.37, 0.69)
Avramopoul
0.16 (-0.08, 0.40)
Strous
-0.42 (-0.85,-0.00)
Strous
-0.70 (-1.62, 0.22)
Zammit
0.18 (-0.07, 0.42)
Flory
0.44 (-0.17, 1.05)
Caspi
0.78 ( 0.09, 1.47)
Wagner
-0.20 (-0.61, 0.22)
Nedic
0.21 (-0.63, 1.06)
Nedic
0.21 (-0.07, 0.50)
Nedic
1.43 ( 0.14, 2.72)
Nedic
0.39 (-0.21, 1.00)
Rujescu
0.10 (-0.14, 0.33)
Perroud
0.17 ( 0.02, 0.32)
Subtotal
0.06 (-0.06, 0.19)
Overall
0.06 (-0.04, 0.17)
-2.7171
0
2.71712
Effect size
59
3. By sample characteristics
Effect size
(95% CI)
Study
General
Albaugh
-0.43 (-0.78,-0.08)
Caspi
-0.03 (-0.14, 0.07)
Kang
0.12 (-0.17, 0.41)
Kang
-0.02 (-0.38, 0.33)
Avramopoul
0.16 (-0.08, 0.40)
Subtotal
-0.02 (-0.18, 0.14)
Psychiatric
Sengupta
0.05 (-0.27, 0.38)
Caspi
0.32 ( 0.01, 0.63)
Caspi
0.43 ( 0.09, 0.77)
Han
-0.25 (-0.55, 0.06)
Han
-0.36 (-0.71,-0.00)
Volavka
0.16 (-0.37, 0.69)
Strous
-0.42 (-0.85,-0.00)
Strous
-0.70 (-1.62, 0.22)
Zammit
0.18 (-0.07, 0.42)
Flory
0.44 (-0.17, 1.05)
Caspi
0.78 ( 0.09, 1.47)
Wagner
-0.20 (-0.61, 0.22)
Rujescu
0.10 (-0.14, 0.33)
Perroud
0.17 ( 0.02, 0.32)
Subtotal
0.06 (-0.09, 0.21)
Substance
Nedic
0.21 (-0.63, 1.06)
Nedic
0.21 (-0.07, 0.50)
Nedic
1.43 ( 0.14, 2.72)
Nedic
0.39 (-0.21, 1.00)
Subtotal
0.31 ( 0.02, 0.61)
Overall
0.06 (-0.04, 0.17)
-2.7171
0
2.71712
Effect size
4. By outcome measure
Effect size
(95% CI)
Study
Aggressiveness
Albaugh
-0.43 (-0.78,-0.08)
Caspi
-0.03 (-0.14, 0.07)
Avramopoul
0.16 (-0.08, 0.40)
Sengupta
0.05 (-0.27, 0.38)
Caspi
0.32 ( 0.01, 0.63)
Caspi
0.43 ( 0.09, 0.77)
Han
-0.25 (-0.55, 0.06)
Han
-0.36 (-0.71,-0.00)
Strous
-0.42 (-0.85,-0.00)
Strous
-0.70 (-1.62, 0.22)
Zammit
0.18 (-0.07, 0.42)
Flory
0.44 (-0.17, 1.05)
Caspi
0.78 ( 0.09, 1.47)
Wagner
-0.20 (-0.61, 0.22)
Nedic
0.21 (-0.63, 1.06)
Nedic
0.21 (-0.07, 0.50)
Nedic
1.43 ( 0.14, 2.72)
Nedic
0.39 (-0.21, 1.00)
Subtotal
0.05 (-0.09, 0.19)
Anger
Kang
0.12 (-0.17, 0.41)
Kang
-0.02 (-0.38, 0.33)
Volavka
0.16 (-0.37, 0.69)
Rujescu
0.10 (-0.14, 0.33)
Perroud
0.17 ( 0.02, 0.32)
Subtotal
0.13 ( 0.02, 0.24)
Overall
0.06 (-0.04, 0.17)
-2.7171
0
2.71712
Effect size
60
COMT Additive
1. By ethnicity (1: caucasian, 0: other)
Effect size
(95% CI)
Study
caucasian==0
Han
1.52 ( 0.18, 2.86)
Han
2.20 ( 0.56, 3.84)
Kang
-0.29 (-1.67, 1.09)
Kang
0.02 (-1.31, 1.35)
Volavka
0.20 (-0.36, 0.76)
Subtotal
0.61 (-0.18, 1.40)
caucasian==1
Caspi
0.10 (-0.43, 0.62)
Avramopoul
-1.96 (-4.40, 0.48)
Caspi
-0.23 (-0.48, 0.02)
Caspi
-2.88 (-5.83, 0.07)
Strous
3.98 ( 1.40, 6.55)
Strous
6.22 ( 0.15, 12.28)
Zammit
-1.11 (-4.22, 1.99)
Flory
-1.26 (-2.65, 0.14)
Caspi
-0.59 (-1.13,-0.05)
Wagner
-0.30 (-2.82, 2.22)
Nedic
-0.05 (-1.96, 1.86)
Nedic
-0.64 (-1.45, 0.16)
Nedic
-1.12 (-3.00, 0.76)
Nedic
-0.74 (-2.00, 0.51)
Rujescu
0.12 (-0.37, 0.61)
Perroud
-0.75 (-1.34,-0.17)
Subtotal
-0.37 (-0.72,-0.02)
Overall
-0.15 (-0.49, 0.19)
-12.283
0
12.2831
Effect size
2. By Age (1: <16, 2: 16-65, 3: >65)
Effect size
(95% CI)
Study
agegroup==1
Caspi
0.10 (-0.43, 0.62)
Caspi
-0.23 (-0.48, 0.02)
Caspi
-2.88 (-5.83, 0.07)
Subtotal
-0.18 (-0.69, 0.34)
agegroup==2
Han
1.52 ( 0.18, 2.86)
Han
2.20 ( 0.56, 3.84)
Kang
-0.29 (-1.67, 1.09)
Kang
0.02 (-1.31, 1.35)
Volavka
0.20 (-0.36, 0.76)
Avramopoul
-1.96 (-4.40, 0.48)
Strous
3.98 ( 1.40, 6.55)
Strous
6.22 ( 0.15, 12.28)
Zammit
-1.11 (-4.22, 1.99)
Flory
-1.26 (-2.65, 0.14)
Caspi
-0.59 (-1.13,-0.05)
Wagner
-0.30 (-2.82, 2.22)
Nedic
-0.05 (-1.96, 1.86)
Nedic
-0.64 (-1.45, 0.16)
Nedic
-1.12 (-3.00, 0.76)
Nedic
-0.74 (-2.00, 0.51)
Rujescu
0.12 (-0.37, 0.61)
Perroud
-0.75 (-1.34,-0.17)
Subtotal
-0.09 (-0.54, 0.35)
Overall
-0.15 (-0.49, 0.19)
-12.283
0
12.2831
Effect size
61
3. By sample characteristics
Effect size
(95% CI)
Study
General
Caspi
0.10 (-0.43, 0.62)
Kang
-0.29 (-1.67, 1.09)
Kang
0.02 (-1.31, 1.35)
Avramopoul
-1.96 (-4.40, 0.48)
Subtotal
-0.02 (-0.48, 0.43)
Psychiatric
Caspi
-0.23 (-0.48, 0.02)
Caspi
-2.88 (-5.83, 0.07)
Han
1.52 ( 0.18, 2.86)
Han
2.20 ( 0.56, 3.84)
Volavka
0.20 (-0.36, 0.76)
Strous
3.98 ( 1.40, 6.55)
Strous
6.22 ( 0.15, 12.28)
Zammit
-1.11 (-4.22, 1.99)
Flory
-1.26 (-2.65, 0.14)
Caspi
-0.59 (-1.13,-0.05)
Wagner
-0.30 (-2.82, 2.22)
Rujescu
0.12 (-0.37, 0.61)
Perroud
-0.75 (-1.34,-0.17)
Subtotal
0.03 (-0.45, 0.51)
Substance
Nedic
-0.05 (-1.96, 1.86)
Nedic
-0.64 (-1.45, 0.16)
Nedic
-1.12 (-3.00, 0.76)
Nedic
-0.74 (-2.00, 0.51)
Subtotal
-0.65 (-1.26,-0.05)
Overall
-0.15 (-0.49, 0.19)
-12.283
0
12.2831
Effect size
4. By outcome measure
Effect size
(95% CI)
Study
Aggressiveness
Caspi
0.10 (-0.43, 0.62)
Avramopoul
-1.96 (-4.40, 0.48)
Caspi
-0.23 (-0.48, 0.02)
Caspi
-2.88 (-5.83, 0.07)
Han
1.52 ( 0.18, 2.86)
Han
2.20 ( 0.56, 3.84)
Strous
3.98 ( 1.40, 6.55)
Strous
6.22 ( 0.15, 12.28)
Zammit
-1.11 (-4.22, 1.99)
Flory
-1.26 (-2.65, 0.14)
Caspi
-0.59 (-1.13,-0.05)
Wagner
-0.30 (-2.82, 2.22)
Nedic
-0.05 (-1.96, 1.86)
Nedic
-0.64 (-1.45, 0.16)
Nedic
-1.12 (-3.00, 0.76)
Nedic
-0.74 (-2.00, 0.51)
Subtotal
-0.14 (-0.62, 0.35)
Anger
Kang
-0.29 (-1.67, 1.09)
Kang
0.02 (-1.31, 1.35)
Volavka
0.20 (-0.36, 0.76)
Rujescu
0.12 (-0.37, 0.61)
Perroud
-0.75 (-1.34,-0.17)
Subtotal
-0.13 (-0.55, 0.30)
Overall
-0.15 (-0.49, 0.19)
-12.283
0
12.2831
Effect size
62
DAT1 Dominant
2. By Age (1: <16, 2: 16-65, 3: >65)
Effect size
(95% CI)
Study
agegroup==1
Jorm
0.06 (-0.09, 0.21)
Caspi
-0.01 (-0.30, 0.28)
Caspi
-0.12 (-0.42, 0.18)
Caspi
-0.16 (-0.25,-0.06)
Subtotal
-0.06 (-0.19, 0.07)
agegroup==2
Gerra
0.31 (-0.27, 0.89)
Caspi
-0.58 (-1.17, 0.01)
Burt
0.02 (-0.25, 0.30)
Subtotal
-0.06 (-0.49, 0.36)
Overall
-0.06 (-0.18, 0.07)
-1.1738
0
Effect size
1.17384
3. By sample characteristics
Study
Effect size
(95% CI)
General
Jorm
Caspi
Burt
Subtotal
0.06 (-0.09, 0.21)
-0.16 (-0.25,-0.06)
0.02 (-0.25, 0.30)
-0.04 (-0.21, 0.12)
Psychiatric
Caspi
Caspi
Caspi
Subtotal
-0.01 (-0.30, 0.28)
-0.12 (-0.42, 0.18)
-0.58 (-1.17, 0.01)
-0.14 (-0.39, 0.11)
Substance
Gerra
Subtotal
0.31 (-0.27, 0.89)
0.31 (-0.27, 0.89)
Overall
-0.06 (-0.18, 0.07)
-1.1738
0
Effect size
1.17384
63
DAT1 Recessive
Effect size
Study
(95% CI)
Jorm
-0.20 (-0.49, 0.09)
Burt
-0.05 (-0.50, 0.41)
Gerra
1.37 ( 0.62, 2.11)
Overall
0.29 (-0.44, 1.02)
-2.7171
0
2.71712
Effect size
DAT1 Additive
Effect size
Study
(95% CI)
Jorm
-0.01 (-0.26, 0.25)
Burt
-0.00 (-0.21, 0.21)
Gerra
-3.57 (-6.30,-0.84)
Overall
-0.07 (-0.45, 0.31)
-12.283
0
12.2831
Effect size
64
DRD4-ex3 Dominant
1. By ethnicity (1: caucasian, 0: other)
Study
Effect size
(95% CI)
caucasian==0
de Young
de Young
Kang
Kang
de Young
Fresan
Subtotal
-0.45 (-1.03, 0.13)
-0.20 (-0.64, 0.24)
-0.17 (-0.49, 0.16)
0.07 (-0.34, 0.49)
-0.20 (-0.85, 0.46)
0.59 ( 0.09, 1.09)
-0.05 (-0.31, 0.21)
caucasian==1
Caspi
Nobile
Dmitrieva
Hohmann
Caspi
Caspi
Zalsman
Caspi
Subtotal
-0.01 (-0.11, 0.09)
-0.02 (-0.19, 0.16)
0.19 (-0.13, 0.51)
0.33 ( 0.10, 0.56)
-0.08 (-0.38, 0.22)
0.19 (-0.11, 0.50)
-0.05 (-0.56, 0.47)
0.14 (-0.46, 0.74)
0.07 (-0.04, 0.17)
Overall
0.04 (-0.06, 0.15)
-1.0885
0
Effect size
1.08852
2. By Age (1: <16, 2: 16-65, 3: >65)
Study
Effect size
(95% CI)
agegroup==1
de Young
Caspi
Nobile
Dmitrieva
Hohmann
Caspi
Caspi
Subtotal
-0.45 (-1.03, 0.13)
-0.01 (-0.11, 0.09)
-0.02 (-0.19, 0.16)
0.19 (-0.13, 0.51)
0.33 ( 0.10, 0.56)
-0.08 (-0.38, 0.22)
0.19 (-0.11, 0.50)
0.06 (-0.07, 0.19)
agegroup==2
de Young
Kang
Kang
de Young
Fresan
Zalsman
Caspi
Subtotal
-0.20 (-0.64, 0.24)
-0.17 (-0.49, 0.16)
0.07 (-0.34, 0.49)
-0.20 (-0.85, 0.46)
0.59 ( 0.09, 1.09)
-0.05 (-0.56, 0.47)
0.14 (-0.46, 0.74)
0.01 (-0.19, 0.21)
Overall
0.04 (-0.06, 0.15)
-1.0885
0
Effect size
1.08852
65
3. By sample characteristics
Study
Effect size
(95% CI)
General
de Young
Caspi
Nobile
Dmitrieva
Hohmann
de Young
Kang
Kang
Subtotal
-0.45 (-1.03, 0.13)
-0.01 (-0.11, 0.09)
-0.02 (-0.19, 0.16)
0.19 (-0.13, 0.51)
0.33 ( 0.10, 0.56)
-0.20 (-0.64, 0.24)
-0.17 (-0.49, 0.16)
0.07 (-0.34, 0.49)
0.02 (-0.11, 0.15)
Psychiatric
Caspi
Caspi
de Young
Fresan
Zalsman
Caspi
Subtotal
-0.08 (-0.38, 0.22)
0.19 (-0.11, 0.50)
-0.20 (-0.85, 0.46)
0.59 ( 0.09, 1.09)
-0.05 (-0.56, 0.47)
0.14 (-0.46, 0.74)
0.10 (-0.10, 0.30)
Overall
0.04 (-0.06, 0.15)
-1.0885
0
Effect size
1.08852
4. By outcome measure
Study
Effect size
(95% CI)
Aggressiveness
de Young
Caspi
Nobile
Dmitrieva
Hohmann
de Young
Caspi
Caspi
de Young
Fresan
Zalsman
Caspi
Subtotal
-0.45 (-1.03, 0.13)
-0.01 (-0.11, 0.09)
-0.02 (-0.19, 0.16)
0.19 (-0.13, 0.51)
0.33 ( 0.10, 0.56)
-0.20 (-0.64, 0.24)
-0.08 (-0.38, 0.22)
0.19 (-0.11, 0.50)
-0.20 (-0.85, 0.46)
0.59 ( 0.09, 1.09)
-0.05 (-0.56, 0.47)
0.14 (-0.46, 0.74)
0.06 (-0.06, 0.18)
Anger
Kang
Kang
Subtotal
-0.17 (-0.49, 0.16)
0.07 (-0.34, 0.49)
-0.07 (-0.33, 0.18)
Overall
0.04 (-0.06, 0.15)
-1.0885
0
Effect size
1.08852
66
MAO-Females Dominant
1. By ethnicity (1: caucasian, 0: other)
Effect size
(95% CI)
Study
caucasian==0
Guo
-0.06 (-0.20, 0.09)
Fresan
0.52 (-0.39, 1.43)
Yang
-0.09 (-0.37, 0.19)
Subtotal
-0.05 (-0.18, 0.07)
caucasian==1
Sjoberg
0.30 (-0.25, 0.84)
Strous
0.04 (-0.77, 0.85)
Kinnally
0.05 (-0.35, 0.45)
Perroud
0.13 (-0.12, 0.38)
Subtotal
0.13 (-0.06, 0.32)
Overall
0.00 (-0.10, 0.11)
-1.4278
0
Effect size
1.42786
2. By Age (1: <16, 2: 16-65, 3: >65)
Effect size
(95% CI)
Study
agegroup==1
Guo
-0.06 (-0.20, 0.09)
Subtotal
-0.06 (-0.20, 0.09)
agegroup==2
Fresan
0.52 (-0.39, 1.43)
Yang
-0.09 (-0.37, 0.19)
Sjoberg
0.30 (-0.25, 0.84)
Strous
0.04 (-0.77, 0.85)
Kinnally
0.05 (-0.35, 0.45)
Perroud
0.13 (-0.12, 0.38)
Subtotal
0.07 (-0.09, 0.23)
Overall
0.00 (-0.10, 0.11)
-1.4278
0
Effect size
1.42786
67
3. By sample characteristics
Effect size
(95% CI)
Study
General
Guo
-0.06 (-0.20, 0.09)
Yang
-0.09 (-0.37, 0.19)
Sjoberg
0.30 (-0.25, 0.84)
Subtotal
-0.05 (-0.17, 0.08)
Psychiatric
Fresan
0.52 (-0.39, 1.43)
Strous
0.04 (-0.77, 0.85)
Kinnally
0.05 (-0.35, 0.45)
Perroud
0.13 (-0.12, 0.38)
Subtotal
0.12 (-0.08, 0.32)
Overall
0.00 (-0.10, 0.11)
-1.4278
0
Effect size
1.42786
4. By outcome measure
Effect size
(95% CI)
Study
Aggressiveness
Guo
-0.06 (-0.20, 0.09)
Sjoberg
0.30 (-0.25, 0.84)
Fresan
0.52 (-0.39, 1.43)
Strous
0.04 (-0.77, 0.85)
Kinnally
0.05 (-0.35, 0.45)
Subtotal
-0.01 (-0.14, 0.11)
Anger
Yang
-0.09 (-0.37, 0.19)
Perroud
0.13 (-0.12, 0.38)
Subtotal
0.03 (-0.19, 0.24)
Overall
0.00 (-0.10, 0.11)
-1.4278
0
Effect size
1.42786
68
MAO-Females Recessive
1. By ethnicity (1: caucasian, 0: other)
Effect size
(95% CI)
Study
caucasian==0
Fresan
0.56 (-0.35, 1.47)
Yang
0.28 (-0.06, 0.62)
Subtotal
0.31 (-0.00, 0.63)
caucasian==1
Sjoberg
0.32 (-0.05, 0.70)
Strous
0.21 (-0.75, 1.18)
Kinnally
0.14 (-0.18, 0.46)
Perroud
-0.03 (-0.20, 0.13)
Subtotal
0.07 (-0.09, 0.23)
Overall
0.13 (-0.03, 0.28)
-1.4725
0
Effect size
1.47252
3. By sample characteristics
Effect size
(95% CI)
Study
General
Yang
0.28 (-0.06, 0.62)
Sjoberg
0.32 (-0.05, 0.70)
Subtotal
0.30 ( 0.05, 0.55)
Psychiatric
Fresan
0.56 (-0.35, 1.47)
Strous
0.21 (-0.75, 1.18)
Kinnally
0.14 (-0.18, 0.46)
Perroud
-0.03 (-0.20, 0.13)
Subtotal
0.02 (-0.12, 0.16)
Overall
0.13 (-0.03, 0.28)
-1.4725
0
Effect size
69
1.47252
4. By outcome measure
Effect size
(95% CI)
Study
Aggressiveness
Sjoberg
0.32 (-0.05, 0.70)
Fresan
0.56 (-0.35, 1.47)
Strous
0.21 (-0.75, 1.18)
Kinnally
0.14 (-0.18, 0.46)
Subtotal
0.24 ( 0.01, 0.47)
Anger
Yang
0.28 (-0.06, 0.62)
Perroud
-0.03 (-0.20, 0.13)
Subtotal
0.09 (-0.21, 0.39)
Overall
0.13 (-0.03, 0.28)
-1.4725
0
Effect size
1.47252
MAO-Females Additive
1. By ethnicity (1: caucasian, 0: other)
Effect size
(95% CI)
Study
caucasian==0
Fresan
-1.80 (-4.50, 0.90)
Yang
-0.26 (-1.37, 0.85)
Subtotal
-0.52 (-1.65, 0.61)
caucasian==1
Sjoberg
-1.05 (-2.22, 0.13)
Strous
-1.04 (-7.81, 5.74)
Kinnally
-0.07 (-0.26, 0.12)
Perroud
-0.07 (-0.79, 0.65)
Subtotal
-0.09 (-0.28, 0.09)
Overall
-0.11 (-0.29, 0.08)
-7.8134
0
Effect size
70
7.81346
3. By sample characteristics
Effect size
(95% CI)
Study
General
Yang
-0.26 (-1.37, 0.85)
Sjoberg
-1.05 (-2.22, 0.13)
Subtotal
-0.63 (-1.44, 0.18)
Psychiatric
Fresan
-1.80 (-4.50, 0.90)
Strous
-1.04 (-7.81, 5.74)
Kinnally
-0.07 (-0.26, 0.12)
Perroud
-0.07 (-0.79, 0.65)
Subtotal
-0.08 (-0.27, 0.11)
Overall
-0.11 (-0.29, 0.08)
-7.8134
0
Effect size
7.81346
4. By outcome measure
Effect size
(95% CI)
Study
Aggressiveness
Sjoberg
-1.05 (-2.22, 0.13)
Fresan
-1.80 (-4.50, 0.90)
Strous
-1.04 (-7.81, 5.74)
Kinnally
-0.07 (-0.26, 0.12)
Subtotal
-0.42 (-1.13, 0.28)
Anger
Yang
-0.26 (-1.37, 0.85)
Perroud
-0.07 (-0.79, 0.65)
Subtotal
-0.12 (-0.73, 0.48)
Overall
-0.11 (-0.29, 0.08)
-7.8134
0
Effect size
71
7.81346
MAO-Males
1. By ethnicity (1: caucasian, 0: other)
Study
Effect size
(95% CI)
caucasian==0
Guo
Manuck
Williams
Fergusson
Fergusson
Fresan
Subtotal
0.17 ( 0.05, 0.28)
0.57 ( 0.02, 1.11)
0.49 ( 0.06, 0.92)
-0.06 (-0.29, 0.17)
-0.47 (-0.91,-0.04)
0.39 (-0.18, 0.96)
0.14 (-0.10, 0.38)
caucasian==1
Kim-Cohen
Manuck
Caspi
Haberstick
Nilsson
Williams
Edwards
Strous
Tikkanen
Perroud
Subtotal
0.20 ( 0.07, 0.34)
0.52 ( 0.12, 0.92)
0.02 (-0.18, 0.21)
0.06 (-0.09, 0.21)
0.10 (-0.35, 0.55)
-0.47 (-0.82,-0.13)
-0.18 (-0.49, 0.13)
0.24 (-0.20, 0.68)
0.14 (-0.16, 0.44)
-0.00 (-0.27, 0.26)
0.06 (-0.07, 0.18)
Overall
0.08 (-0.03, 0.19)
-1.1130
0
Effect size
1.11307
2. By Age (1: <16, 2: 16-65, 3: >65)
Study
Effect size
(95% CI)
agegroup==1
Guo
Kim-Cohen
Subtotal
0.17 ( 0.05, 0.28)
0.20 ( 0.07, 0.34)
0.18 ( 0.10, 0.27)
agegroup==2
Manuck
Williams
Fergusson
Fergusson
Fresan
Manuck
Caspi
Haberstick
Nilsson
Williams
Edwards
Strous
Tikkanen
Perroud
Subtotal
0.57 ( 0.02, 1.11)
0.49 ( 0.06, 0.92)
-0.06 (-0.29, 0.17)
-0.47 (-0.91,-0.04)
0.39 (-0.18, 0.96)
0.52 ( 0.12, 0.92)
0.02 (-0.18, 0.21)
0.06 (-0.09, 0.21)
0.10 (-0.35, 0.55)
-0.47 (-0.82,-0.13)
-0.18 (-0.49, 0.13)
0.24 (-0.20, 0.68)
0.14 (-0.16, 0.44)
-0.00 (-0.27, 0.26)
0.06 (-0.08, 0.19)
Overall
0.08 (-0.03, 0.19)
-1.1130
0
Effect size
1.11307
72
3. By sample characteristics
Study
Effect size
(95% CI)
General
Guo
Kim-Cohen
Manuck
Williams
Fergusson
Fergusson
Manuck
Caspi
Haberstick
Nilsson
Williams
Edwards
Subtotal
0.17 ( 0.05, 0.28)
0.20 ( 0.07, 0.34)
0.57 ( 0.02, 1.11)
0.49 ( 0.06, 0.92)
-0.06 (-0.29, 0.17)
-0.47 (-0.91,-0.04)
0.52 ( 0.12, 0.92)
0.02 (-0.18, 0.21)
0.06 (-0.09, 0.21)
0.10 (-0.35, 0.55)
-0.47 (-0.82,-0.13)
-0.18 (-0.49, 0.13)
0.06 (-0.07, 0.19)
Psychiatric
Fresan
Strous
Perroud
Subtotal
0.39 (-0.18, 0.96)
0.24 (-0.20, 0.68)
-0.00 (-0.27, 0.26)
0.10 (-0.11, 0.31)
Substance
Tikkanen
Subtotal
0.14 (-0.16, 0.44)
0.14 (-0.16, 0.44)
Overall
0.08 (-0.03, 0.19)
-1.1130
0
1.11307
Effect size
4. By outcome measure
Study
Effect size
(95% CI)
Aggressiveness
Guo
Kim-Cohen
Manuck
Williams
Fergusson
Fergusson
Manuck
Caspi
Haberstick
Nilsson
Williams
Edwards
Fresan
Strous
Tikkanen
Subtotal
0.17 ( 0.05, 0.28)
0.20 ( 0.07, 0.34)
0.57 ( 0.02, 1.11)
0.49 ( 0.06, 0.92)
-0.06 (-0.29, 0.17)
-0.47 (-0.91,-0.04)
0.52 ( 0.12, 0.92)
0.02 (-0.18, 0.21)
0.06 (-0.09, 0.21)
0.10 (-0.35, 0.55)
-0.47 (-0.82,-0.13)
-0.18 (-0.49, 0.13)
0.39 (-0.18, 0.96)
0.24 (-0.20, 0.68)
0.14 (-0.16, 0.44)
0.09 (-0.03, 0.20)
Anger
Perroud
Subtotal
-0.00 (-0.27, 0.26)
-0.00 (-0.27, 0.26)
Overall
0.08 (-0.03, 0.19)
-1.1130
0
Effect size
1.11307
73
TPH Dominant
1. By ethnicity (1: caucasian, 0: other)
Study
Effect size
(95% CI)
caucasian==0
Manuck
Kim
Kim
Evans
Subtotal
-0.11 (-0.46, 0.23)
0.17 (-0.54, 0.87)
0.44 (-0.06, 0.94)
0.24 (-0.04, 0.51)
0.16 (-0.07, 0.39)
caucasian==1
Reuter
Staner
Burt
New
Zalsman
Staner
Perroud
Subtotal
-0.08 (-0.43, 0.28)
0.54 (-0.38, 1.46)
0.17 (-0.21, 0.54)
-0.56 (-2.03, 0.90)
0.18 (-0.38, 0.73)
0.43 (-0.29, 1.15)
-0.01 (-0.19, 0.17)
0.04 (-0.10, 0.17)
Overall
0.08 (-0.03, 0.19)
-2.0314
0
Effect size
2.03142
3. By sample characteristics
Study
Effect size
(95% CI)
General
Manuck
Reuter
Staner
Burt
Subtotal
-0.11 (-0.46, 0.23)
-0.08 (-0.43, 0.28)
0.54 (-0.38, 1.46)
0.17 (-0.21, 0.54)
0.01 (-0.19, 0.21)
Psychiatric
Kim
Kim
Evans
New
Zalsman
Staner
Perroud
Subtotal
0.17 (-0.54, 0.87)
0.44 (-0.06, 0.94)
0.24 (-0.04, 0.51)
-0.56 (-2.03, 0.90)
0.18 (-0.38, 0.73)
0.43 (-0.29, 1.15)
-0.01 (-0.19, 0.17)
0.11 (-0.03, 0.24)
Overall
0.08 (-0.03, 0.19)
-2.0314
0
Effect size
2.03142
74
4. By outcome measure
Study
Effect size
(95% CI)
Aggressiveness
Manuck
Reuter
Staner
Burt
New
Zalsman
Staner
Subtotal
-0.11 (-0.46, 0.23)
-0.08 (-0.43, 0.28)
0.54 (-0.38, 1.46)
0.17 (-0.21, 0.54)
-0.56 (-2.03, 0.90)
0.18 (-0.38, 0.73)
0.43 (-0.29, 1.15)
0.05 (-0.14, 0.23)
Anger
Kim
Kim
Evans
Perroud
Subtotal
0.17 (-0.54, 0.87)
0.44 (-0.06, 0.94)
0.24 (-0.04, 0.51)
-0.01 (-0.19, 0.17)
0.14 (-0.06, 0.33)
Overall
0.08 (-0.03, 0.19)
-2.0314
0
Effect size
2.03142
TPH Recessive
1. By ethnicity (1: caucasian, 0: other)
Study
Effect size
(95% CI)
caucasian==0
Manuck
Kim
Kim
Evans
Subtotal
-0.05 (-0.32, 0.21)
-0.10 (-0.78, 0.58)
0.34 (-0.17, 0.86)
0.22 ( 0.00, 0.45)
0.12 (-0.07, 0.30)
caucasian==1
Rujescu
Reuter
Staner
Burt
New
Zalsman
Staner
Perroud
Subtotal
0.14 (-0.14, 0.42)
-0.37 (-0.63,-0.12)
0.05 (-0.81, 0.91)
0.19 (-0.10, 0.48)
0.98 ( 0.07, 1.89)
0.18 (-0.29, 0.64)
-0.04 (-0.63, 0.56)
-0.08 (-0.22, 0.06)
0.02 (-0.17, 0.22)
Overall
0.05 (-0.09, 0.19)
-1.8894
0
Effect size
1.88944
75
3. By sample characteristics
Study
Effect size
(95% CI)
General
Manuck
Rujescu
Reuter
Staner
Burt
Subtotal
-0.05 (-0.32, 0.21)
0.14 (-0.14, 0.42)
-0.37 (-0.63,-0.12)
0.05 (-0.81, 0.91)
0.19 (-0.10, 0.48)
-0.03 (-0.26, 0.21)
Psychiatric
Kim
Kim
Evans
New
Zalsman
Staner
Perroud
Subtotal
-0.10 (-0.78, 0.58)
0.34 (-0.17, 0.86)
0.22 ( 0.00, 0.45)
0.98 ( 0.07, 1.89)
0.18 (-0.29, 0.64)
-0.04 (-0.63, 0.56)
-0.08 (-0.22, 0.06)
0.12 (-0.08, 0.32)
Overall
0.05 (-0.09, 0.19)
-1.8894
0
Effect size
1.88944
4. By outcome measure
Study
Effect size
(95% CI)
Aggressiveness
Manuck
Rujescu
Reuter
Staner
Burt
New
Zalsman
Staner
Subtotal
-0.05 (-0.32, 0.21)
0.14 (-0.14, 0.42)
-0.37 (-0.63,-0.12)
0.05 (-0.81, 0.91)
0.19 (-0.10, 0.48)
0.98 ( 0.07, 1.89)
0.18 (-0.29, 0.64)
-0.04 (-0.63, 0.56)
0.04 (-0.17, 0.25)
Anger
Kim
Kim
Evans
Perroud
Subtotal
-0.10 (-0.78, 0.58)
0.34 (-0.17, 0.86)
0.22 ( 0.00, 0.45)
-0.08 (-0.22, 0.06)
0.08 (-0.14, 0.31)
Overall
0.05 (-0.09, 0.19)
-1.8894
0
Effect size
1.88944
76
TPH Additive
1. By ethnicity (1: caucasian, 0: other)
Study
Effect size
(95% CI)
caucasian==0
Manuck
Kim
Kim
Evans
Subtotal
0.22 (-0.50, 0.93)
-0.12 (-2.54, 2.29)
-1.36 (-2.78, 0.07)
-1.13 (-2.12,-0.14)
-0.57 (-1.47, 0.33)
caucasian==1
Reuter
Staner
Burt
New
Zalsman
Staner
Perroud
Subtotal
0.45 ( 0.06, 0.85)
-0.70 (-2.57, 1.16)
-0.14 (-0.34, 0.06)
-2.18 (-5.90, 1.54)
-0.93 (-3.18, 1.32)
-0.59 (-2.60, 1.43)
0.23 (-0.35, 0.81)
0.04 (-0.31, 0.40)
Overall
-0.12 (-0.46, 0.23)
-5.9017
0
Effect size
5.90176
3. By sample characteristics
Study
Effect size
(95% CI)
General
Manuck
Reuter
Staner
Burt
Subtotal
0.22 (-0.50, 0.93)
0.45 ( 0.06, 0.85)
-0.70 (-2.57, 1.16)
-0.14 (-0.34, 0.06)
0.10 (-0.30, 0.51)
Psychiatric
Kim
Kim
Evans
New
Zalsman
Staner
Perroud
Subtotal
-0.12 (-2.54, 2.29)
-1.36 (-2.78, 0.07)
-1.13 (-2.12,-0.14)
-2.18 (-5.90, 1.54)
-0.93 (-3.18, 1.32)
-0.59 (-2.60, 1.43)
0.23 (-0.35, 0.81)
-0.60 (-1.29, 0.09)
Overall
-0.12 (-0.46, 0.23)
-5.9017
0
Effect size
5.90176
77
4. By outcome measure
Study
Effect size
(95% CI)
Aggressiveness
Manuck
Reuter
Staner
Burt
New
Zalsman
Staner
Subtotal
0.22 (-0.50, 0.93)
0.45 ( 0.06, 0.85)
-0.70 (-2.57, 1.16)
-0.14 (-0.34, 0.06)
-2.18 (-5.90, 1.54)
-0.93 (-3.18, 1.32)
-0.59 (-2.60, 1.43)
0.03 (-0.33, 0.40)
Anger
Kim
Kim
Evans
Perroud
Subtotal
-0.12 (-2.54, 2.29)
-1.36 (-2.78, 0.07)
-1.13 (-2.12,-0.14)
0.23 (-0.35, 0.81)
-0.56 (-1.50, 0.38)
Overall
-0.12 (-0.46, 0.23)
-5.9017
0
Effect size
5.90176
AR (CAG)
Effect size
Study
(95% CI)
Aluja
-0.14 (-0.47, 0.20)
Westberg
1.73 ( 1.07, 2.40)
Aluja
-0.69 (-1.09,-0.29)
Westberg
0.25 (-0.09, 0.58)
Overall
0.24 (-0.50, 0.99)
-2.7171
0
Effect size
78
2.71712
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