BIOLOGICAL SENSITIVITY & DEVELOPMENT:
STUDYING GENES & ENVIRONMENTS IN THE FRAGILE FAMILIES
STUDY
Jeanne Brooks-Gunn
Virginia & Leonard Marx Professor of Child Development
Teachers College & the College of Physicians and Surgeons
Columbia University
November 2012
Collaborators:
Sara Mclanahan
Colter Mitchell
Irwin Garfinkel
John Hobcraft
Daniel Notterman
Individuals vary in their genetic sensitivity to environments so
that more genetic sensitivity results in more negative outcomes
in unfavorable environments (Diathesis-Stress Model) and
more positive outcomes in favorable environments.
2
Unfavorable Environment
Negative
Outcome
Sensitive gene markers
Not-sensitive gene markers
3
Environment
Unfavorable
Favorable
Outcome
Negative
Sensitive gene markers
Not sensitive gene markers
4
Severe
Negative
Neutral
Outcome
Negative
Sensitive gene markers
Not sensitive gene markers
5
Individual changes in
o Biology
o Cognition
o Psychology
Individual environmental events
o Type
o Timing
o Sequencing
o Cumulating
o Change
6
Responses to early events may carry forward into subsequent behavior and
responses to the environment for genetically sensitive individuals.
Or
Responses to current environmental events may be more pronounced and/or
may influence the ability to recover from an event for genetically sensitive
individuals.
7
•
•
•
•
•
•
•
•
Perinatal
Infant/toddler
Early childhood
Childhood
Early adolescence
Adolescence
Early adulthood
Adulthood
Preschool
Primary School
Secondary School
Post-Secondary School
Post School
8
1
Passive
Genotypes and environment correlated
2
Evocative
Environment reacts to genotype
3
Active
Individuals, based on their genotype, select their environment
1
rGE
2
3
0-5
6-10
11-15
Age
16-20
21-25
9
Passive rGE
r =.50
maternal reading & child vocabulary
r = .25
maternal education is controlled
r = .15
maternal language ability is also controlled
10
Evocative rGE
Reading
Vocabulary
1
2
3
Age of Child
Source: Early Head Start
11
Evocative rGE
Spanking
Aggression
1
3
5
Age of Child
Source: Fragile Families; Mackenzie
At age 1, mother reported on whether child had a different temperament, not on aggression
12
Wellbeing/Positive Health
I
II
Unfavorable
Environments
Favorable
Environments
IV
III
Illness
13
3
Probability
of PPD
2
1
0
8
12
10
14
16
Years of Education
Number of Reactive Alleles
0 or 1
95% Cl
3 or 4
14
Birth cohort through age 9
Multi-method
Probability sample of 4,898 births
•
•
•
•
•
•
20 U.S. cities (populations of 200,000 or more)
75 hospitals
Roughly 3,700 non-marital births; 1,200 marital births
15
Fragile Families Timeline
16
Fragile Families Study Components
17
Year
2
2
1
1
1
1
1
1
1
1
1
1
1
1
0
0
9
9
9
9
9
9
9
9
9
9
9
9
0
0
9
9
8
8
7
7
6
6
5
5
4
4
5
0
5
0
5
0
5
0
5
0
5
0
5
0
Percent
40
35
30
25
20
15
10
5
0
• What are the capabilities and circumstances of unmarried parents?
• What is the nature of parental relationships at birth, and how do
relationships change over time?
• How do family structure and stability affect parental resources,
investments, and child wellbeing?
50
40
30
20
10
0
Teen parent
Mothers Married Less than high High school or Some college
school
equivalent
Fathers Married
Mothers Unmarried
College or
higher
Fathers Unmarrie
40
30
20
10
0
Depression
Mothers Married Fathers Married
Father incarcerated
Mothers Unmarried
Fathers Unmarried
100
90
80
Percent
70
60
50
40
30
20
10
0
End Relationship
with Bio Dad
Married
Cohab
Visit
Begin New
Partnership
No Rel
Child with New
Partner
Number of Transitions by Year 5
(Unmarried Parents)
•
•
•
•
Age 9
Oragene DNA Self-Collection Kits
Sent to Notterman lab @ Princeton from Westat
(interviewers)
DNA extracted, quality tested, and divided into aliquots for
storage.
24
Of participants of in-home visit
Mothers 79% (n=2,670)
Children 85% (n=2,884)
•
•
•
•
•
•
•
Hispanics-91% , White-86%, Black-82%
Immigrant Mothers-89%
Geography: NE-80%, South-84%, West-90%, Midwest-85%
Child is female-86%
25
•
Serotonin: 5-HTT (5-HTTLPR and Stin2)
•
Dopamine: DRD4, DRD2, DAT1, and COMT
•
Obesity: FTO, MC4R, BDNF, TMEM18
•
Others: MAOA (n=788), OXTR (n=900)
26
5-HTT POLYMORPHISMS
B. STin 2
0
0
.1
.1
.2
Proportion
.3
Proportion
.2
.3
.4
.4
.5
A. 5- HTTLPR
LL
SS
LS
10.10
12.12
10.12
27
5-HTTLPR Genotype Frequency
Hispanic
Black
Other
Hispanic
Blac k
Other
40
40
0
40
60
Percent
20
20
0
60
40
20
20
0
0
Percent
White
60
60
White
STin2 Genotype Frequency
LL
LS
SS
LL
LS
SS
10/10 10/12 12/12
10/10 10/12 12/12
Mother's race (self-report)
28
Do genes moderate the impact of the SES
on postpartum depression?
Genes: Serotonin (5-HTT: 5-HTTLPR and Stin2)
SES: Mother’s education, income, and parent’s education
Outcome: Major depressive episode in year after birth
29
0
10
Percent
20
30
40
C. Number of Reactive Alleles
0
1
2
Number of S or 12 Alleles
3
4
30
3
Probability
of PPD
2
1
0
8
12
10
14
16
Years of Education
Number of Reactive Alleles
0 or 1
95% Cl
3 or 4
31
31
Do genes moderate the impact of the
recession on parents’ aggressive
parenting?
Gene: Dopamine (DRD2 Taq1a)
Environment: Exposure to the Great Recession
Outcome: Harsh Parenting
32
T variant is sensitive variant
33
Do genes moderate the impact of family
instability on children
Family instability: Biological father exits and entrances
Outcome: Child externalizing behavior (rule breaking, aggression)
34
• Dopamine
• 4 Different Genes
• DRD2, DRD4, Dat1, COMT
• Serotonin
• Serotonin Transporter Gene: 5-HTT
• 5-HTTLPR, STin2
Dopamine
30
Percent
25
20
15
10
5
0
0
1
2
3
4
5
Reactive Alleles
6
7
8
36
• Mother’s Reports of Relationship Status With Biological
Father
•
•
•
•
Baseline, 1 year, 3 years, 5 years, 9 years
Entered a residential relationship
Exited a residential relationship
Did not change residential relationship
•
•
•
•
•
•
•
Mother’s race
Mother’s baseline education
Mother’s age at baseline
Baseline household income
Father’s residence at birth
Child birth order
Child low birth weight
Externalizing
Year
3
Year
5
Year 9
Slope
Genes
Controls
Intercept
0-1
1-3
3-5
Family Instability
5-9
Externalizing
Year
3
Year
5
Year 9
Slope
Genes
Controls
Intercept
0-1
1-3
3-5
Family Instability
5-9
Externalizing
Year
3
Year
5
Year 9
Slope
Genes
Controls
Intercept
0-1
1-3
3-5
Family Instability
5-9
Externalizing
Year
3
Year
5
Year 9
Slope
Genes
Controls
Intercept
0-1
1-3
3-5
Family Instability
5-9
Externalizing
Year
3
Year
5
Year 9
Slope
Genes
Controls
Intercept
0-1
1-3
3-5
Family Instability
5-9
Dopamine
0-8
Serotonin
0-4
Exit
0.45*
0.82*
Enter
-0.57*
-0.48
Father Residential Change Between 0-1 on Age 9
Externalizing-Boys
4
Exit
Difference in Externalizing
3
Enter
2
1
0
-1
-2
-3
-4
0-2
3
4
5
6-8
# of Reactive Dopamine Alleles
46
Father Residential Change Between 0-1 on Age 9
Externalizing-Girls
3
Exit
Difference in Externalizing
2.5
Enter
2
1.5
1
0.5
0
-0.5
-1
-1.5
-2
-2.5
0-2
3
4
5
# of Reactive Dopamine Alleles
6-8
4
Father Residential Change Between 0-1 on Age 5
Externalizing-Boys
Exit
Difference in Externalizing
3
Enter
2
1
0
-1
-2
-3
-4
0-2
3
4
5
# of Reactive Dopamine Alleles
6-8
49
Do “obesity” genes have similar effects for mothers and children
in trajectories of BMI?
Genes: FTO (rs9939609), MC4R (rs), BDNF (rs6265), TMEM18
(rs6548238)
Outcome: BMI, Percentiles, Obesity at 3, 5, and 9 years
50
BMI
Year 3
Year 5
Year 9
Intercept
Slope
Genes
Controls
51
Mom
3
Child
2.5
Effect on BMI
2
1.5
1
0.5
0
-0.5
FTO-A
BDNF-Val TMEM18-C
Genes
MC4R
52
Dopamine receptor genes (Chr.11)
• DRD2; rs 1800497
• 10kb upstream in ANKK1 gene
• T or C
• T allele higher impulsivity/addiction
• DRD4; rs 1800955
• T or C
• C allele higher novelty seeking
Dopamine Transporter gene (Chr.5)
Gene associated with ADHD, impulsivity, some depression
rs 40184; Intron 14
T or C: T allele higher depression
Coding region
L
HTTLPR
- 44 bp
The S allele = higher rates of mood disorders
S
5-HTTLPR
Coding region
10 Repeats
5-HTTLPR
12 Repeats
The 12 repeat = higher rates of mood disorders
Percent
70
Low education
60
Middle education
50
High education
40
30
20
10
0
1960
1970
1980
Year
Figure 2, McLanahan, 2004
1990
2000
Single Mothers
(US Census)
60
Low education
50
M iddle education
Percent
High education
40
30
20
10
0
1960
1970
1980
Year
Figure 3, McLanahan, 2004
1990
2000
Divorce (SIIP)
40
35
No 4-year degree
4-year degree
Percent
30
25
20
15
10
5
0
1960-64
1965-69
1970-74
1975-79
Year
Figure 4, McLanahan, 2004
1980-84
1984-89
Dollars
Median Family Income (US Census)
Low Education
90,000
80,000
70,000
60,000
50,000
40,000
30,000
20,000
10,000
0
M iddle Education
High Education
1960
1970
1980
Year
Figure 6, McLanahan, 2004
1990
2000