Figure S1. Manhattan and QQ plots for AD-AUDIT GWAS
Figure S2. Regional association plot showing signal around 4q34.1 for AD-AUDIT GWAS
Figure S3. Regional association plot showing signal around 6q25.1 for AD-AUDIT GWAS
Figure S4. Regional association plot showing signal around 7p14.1 for AD-AUDIT GWAS
Supplementary Table 1. Overview of previously published GWASs for Alcohol dependence
First author/
Date/Journal/Title
Treutlein,
July 2009,
Arch Gen Psychiatry,
Genome-wide
association study of
alcohol dependence
Bierut,
March 2010,
PNAS,
A genome-wide
association study of
alcohol dependence
Edenberg,
May 2010,
Alcohol Clin Exp Res
Genome-wide
association study of
alcohol dependence
implicates a region in
chromosome 11
Wang,
March 2011,
J Neural Transm,
Family-based
association analysis of
alcohol dependence in
the COGA sample and
replication in the
Australian twinfamily
Kendler,
May 2011,
Alcohol Clin Exp Res,
Genomewide
association analysis of
symptoms of alcohol
dependence in the
Original study
design/
Population
487 cases
1358 controls
German (men)
Replication
study design/
Population
1024 cases
996 controls
German
(male)
Alcohol
dependence
diagnosis
DSM-IV AD
SNP platform/
Imputation
reference
Illumina 550
Genome-wide significant
association
SNPs (Pvalue < 5x10-8)
rs7590720 (P= 9.72 x 10-9)
rs1344694 (P=1.69x 10-8)
1897 cases
1932 controls
EAs1 & AAs2
from SAGE3
258 family
pedigrees EAs
from COGA4
487 cases
1358 controls
German men
262 family
pedigrees 59
family trios
EAs
from COGA
DSM-IV AD
Illumina 1M
No SNPs replicated (P < 0.05) in
the replication samples
DSM-IV AD
Illumina 1M
778 Australian
nuclear families
(1650 AD)
from OZALC5
DSM-IV AD
847 cases
552 controls
EAs
345 cases
140 controls
AAs
from COGA
116 Caucasian
pedigrees from
COGA
2357 EAs
812 AAs
from MGS26
Gene (region)
Suggestive association
SNPs (Pvalue > 5x10-8)
Gene (region)
2q35
2q35
rs705648 (P = 1.78 x 10-6)
rs1614972 (P = 1.41 x 10-4)
rs13362120 (P = 1.85 x 10-5)
rs13160562 (P = 7.09 x 10-6)
rs1864982 (P = 3.46 x 10-6)
rs6902771 (P = 8.3 x 10-6)
rs729302 (P = 4.02 x 10-5)
rs13273672 (P = 4.75 x 10-4)
rs1487814 (P = 3.49 x 10-5)
rs7138291 (P = 3.68 x 10-5)
rs36563 (P = 4.57 x 10-6)
rs11640875 (P = 1.84 x 10-5 )
rs12388359 (P = 3.57 x 10-6)
15 SNPs with P < 10-5 in the
discovery stage (see Treutlein et al.)
PECR (2q35)
ADH1C (4q23)
CAST (5q15)
CAST (5q15)
PPP2R2B (5q32)
ESR1 (6q25.1)
7q32.1
GATA4 (8p23.1)
11p14.3
CCDC41 (12q22)
14q24.2
CDH13 (16q23.3)
Xp22.2
rs2583442 (P = 1.2 x 10-4)
SLC22A18, PHLDA2
(11p15.5)
NAP1L4,
SNORA54 (11p15.5)
CARS (11p15.5)
OSBPL5 (11p15.5)
-5
rs3814964 (P = 7.4 x 10 )
rs7481584 (P = 9.5 x 10-5)
rs4758533 (P = 4.8 x 10-5)
Symptoms of AD
(factor analysis)
COGA
Affymetrix 10k
Australian
Illumina 370k
Affymetrix 6.0
Australian
rs7119734 (P= 3.75 x 10-8)
rs2298767 (P= 6.34 x 10-9 )
rs10892169 (P= 5.3 x 10-9)
rs3851576 (P= 3.62 x 10-8)
No SNPs reached gws threshold
DSCAML1
(11q23)
COGA
rs1986644 (P= 8.51 x 10-6)
rs532342 (P= 1.07 x 10-5)
rs1367311 (P= 2.31 x 10-6)
rs979606 (P= 4.14 x10-4)
Australian
rs637547 (P= 5.11 x 10-7)
24 SNPs with suggestive
association (see Kendler et al.)
EDNRB (13q22)
USH2A (1q41)
TIPARP (3q25.31)
MAOA (Xp11.3)
NKAIN2 (6q21)
molecular genetics of
schizophrenia
(MGS2) control
sample
Heath,
September 2011,
Biol Psychiatry,
A quantitative-trait
genome-wide
association study of
alcoholism risk in the
community : findings
and implications
Zuo,
November 2011,
PLoS one,
A novel, functional
and replicable risk
gene region for
alcohol dependence
identified by genomewide association study
Frank,
January 2012,
Addict Biol,
Genome-wide
significant association
between alcohol
dependence and a
variant in the ADH
gene cluster
Zuo,
January 2012,
Neuropsychopharmac
ology,
Genome-wide
association study of
alcohol dependence
implicates KIAA0040
on chromosome 1q
Zuo,
May 2013,
Drug and alcohol
dependence,
NKKAIN1-SERINC2
is a functional,
replicable and
genome-wide
2062 AD cases
from OZALC
681 cases
508 controls
AAs
From SAGE &
COGA
1409 cases
1518 controls
EAs from COGA
& SAGE
6438 Australian
family Ss from
OZLAC
1333 cases
2168 controls
German men
Heaviness of
Drinking factor
score
Alcohol
dependence factor
Illumina 370k
No SNPs reached gws threshold
DSM-IV AD
Illumina 1M
One LD block containing 30
SNPS replicable risk SNPs
around rs9294269
PHF3-PTP4A1
(6q12)
ADH1B-ADH1C
(4q23)
5Mb region
imputed using
1kG and
HapMap3 CEU
for Australian Ss
DSM-IV AD
Illumina 550
rs1789891 (P= 1.27 x 10-8)
Meta-analysis
SAGE & COGA
1409 cases EAs
1518 controls
EAs
681 cases AAs
508 controls AAs
From SAGE &
COGA
DSM-IV AD
Illumina 1M
No SNPs reached gws threshold
1409 cases EAs
1518 controls
EAs
from COGA &
SAGE
6438 Australian
family Ss with
1645 AD cases
From OZALC
DSM-IV AD
SAGE & COGA
Illumina 1M
OZALC
Illumina 370k
rs1039630 (P= 4.7 x 10-8)
rs4478858 (P= 3.1 x 10-8)
rs2275436 (P= 3.8 x 10-8)
NKAIN1SERINC2 (1p35)
several SNPs with suggestive
association (see Heath et al.)
TMEM108 (3q21)
ANKS1A (6p21.31)
rs1344694 (P= 4.59 x 10-6)
rs9825310 (P= 7.55 x 10-6)
rs7694974 (P= 4.4 x 10-6)
rs6818421 (P= 4.61 x10-6)
rs1000579 (P= 4.01 x 10-7)
rs4770403 (P= 6.43 x 10-6)
rs2810114 (P= 4.39 x 10-6)
2q35
3p22.3
4p16
4p16
4p16
13q12
14q24
several SNPs with suggestive
association (see Zuo et al.)
association with KIAA0040
overlapped in EA and AA
KIAA0040 (1q24-q25)
significant risk gene
region specific for
alcohol dependence in
subjects of European
descent
Park,
June 2013
Hum Genet,
Extended genetic
effects of ADH cluster
genes on the risk of
alcohol dependence :
from GWAS to
replication
117 cases
279 controls
Korean
504 cases
471 controls
Korean
DSM-IV AD
Illumina 660
Wang,
November 2013,
Molecular Psychiatry,
A genome-wide
association study of
alcohol dependence
symptom counts in
extended pedigrees
identifies C15orf53
118 extended
families
684 cases
964 controls
from COGA
SAGE: 2647 Ss
Australia
(OZALC): 6166
Ss
Quantitative
endophenotype:
symptom count.
Dichotomous
phenotype: DSMIV AD
Illumina Human
OmniExpress
Han,
December 2013,
Am J Hum Genet,
Integrating GWASs
and human protein
interaction networks
identifies a gene
subnetwork
underlying alcohol
dependence
Gelernter,
January 2014,
Molecular psychiatry,
Genome-wide
association study of
alcohol dependence:
significant findings in
African- and EAs
including novel risk
loci
COGA + SAGE
2670 EAs
1453 cases
1217 controls
1150 AAs
708 cases
442 controls
OZALC
795 cases
641 controls
DSM-IV AD
Illumina 1M
Illumina 370k
Illumina
HumanOmini1Quad
2379 EAs
3318 AAs
From SAGE
1746 EAs
803 AAs
German
1806 cases
1978 controls
DSM-IV AD and
symptoms counts
ordinal trait
Illumina 1M
Yale Penn
1641 cases
1367 controls
Imputation 1kG
rs1229984 (P=2.63 x 10-21)
rs1442492 (P=2.01 x 10-16)
rs284787 (P=1.75 x 10-15)
rs284784 (P= 2.43 x 10-15)
rs975833 (P= 1.12 x 10-14)
rs2075633 (P= 6.67 x 10-14)
rs284793 (P= 2.99 x 10-12)
rs729147 (P=3.84 x10-11)
rs894369 (P=3.84 x10-11)
rs994771 (P=4.76 x 10-11)
rs2851300 (P=9.88 x10-10)
rs4147531 (P=1.45x10-9)
rs4147532 (P=1.6 x10-9)
rs12912251 (P= 4.5 x 10-8,
inflation corrected P= 9.4 x 10-7,
nominal association in the
replication sample SAGE)
ADH1B (4q22)
ADH7 (4q23)
ADH7 (4q23)
ADH1A (4q23)
ADH1B (4q23)
ADH1B (4q23)
4q22-q23
4q22-q23
ADH7 (4q23)
ADH1A (4q23)
ADH1A (4q23)
ADH1A (4q23)
ADH1A (4q23)
C15orf53 (15q14)
several SNPs with suggestive
association (see Park et al.)
several SNPs with suggestive
association (see Wang et al.)
rs10914375 (P= 1.9 x 10-7)
rs7182484 (P=3.5 x10-7)
rs1229984 (P=1.81x10-30)
rs2066702 (P=1.5x10-13)
rs28542574(P=3.62 x10-11)
rs17028615(P=2.88 x10-8)
rs10031423(P=2.01x10-8)
rs58521602 (P=3.35x10-8)
rs1437396 (P=1.17x10-10)
ADH1B (4q23)
ADH1B (4q23)
LOC100507053
LOC100507053
PDLIM5 (4q22)
METAP (4q23)
MTIF2-CCDC88A
(2p16.1)
rs1493464 (P=8.59x10-9)
5p15.33
several SNPs with suggestive
association (see Gelernter et al.)
SERINC2 (1p35.1)
15q14
rs1856202 (P=5.99x10-11)
rs59514816 (P=2.89x10-8)
Wetherill,
February 2014,
Alcohol Clin exp Res,
Family-based
association analysis of
alcohol dependence
criteria and severity
1
118 extended EAs
families from
COGA
2647 Ss EAs from
SAGE
European-Americans ancestry
African-Americans ancestry
3
The Study of Addiction: Genetics and Environment
4
The Collaborative Study on the Genetics of Alcoholism
5
The Australian twin-family study of alcohol use disorder
6
The Molecular Genetics of Schizophrenia 2
2
Latent class
analysis derived
from DSM-IV
AD
Illumina Human
OmniExpress
Illumina 1M
9p13.3
DPP9 (19p13.3)
rs11035102 (P=7.3 x 10-8)
rs17484734 (P=4.1 x 10-8)
absence of replication P > 0.05 (see
Wetherill et al.)
OR51L1 (11p15.4)
NALCN (13q32.3)