Table 4.
Associations Between Early Life Socioeconomic Position and Candidate Gene Methylation by “Cumulative Effects” Model, Jerusalem Perinatal Family Follow-up Study, 1974–2009
| Model |
ABCA1
|
HSD11B2
|
INS-IGF2
|
LEP
|
NR3C1
|
||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| β Coefficient | 95% CI | P Value | β Coefficient | 95% CI | P Value | β Coefficient | 95% CI | P Value | β Coefficient | 95% CI | P Value | β Coefficient | 95% CI | P Value | |
| High (Classes 1–3) Versus Low (Classes 4–6) Paternal Occupational Class a | |||||||||||||||
| Multivariable, observables b | 0.4 | −1.1, 1.9 | 0.6 | 0.004 | −0.4, 0.4 | 1.0 | 0.3 | −0.7, 1.3 | 0.5 | 0.6 | −1.8, 3.0 | 0.6 | −0.4 | −0.9, 0.08 | 0.1 |
| Multivariable, constructed scores c | 0.4 | −1.0, 1.9 | 0.6 | −0.02 | −0.4, 0.4 | 0.9 | 0.2 | −0.8, 1.1 | 0.7 | 0.8 | −1.5, 3.0 | 0.5 | −0.5 | −1.0, 0.02 | 0.06 |
| Inverse probability weighted, constructed scores d | 1.0 | −0.5, 2.5 | 0.2 | −0.2 | −0.6, 0.2 | 0.4 | 0.2 | −0.8, 1.2 | 0.7 | 1.0 | −1.6, 3.7 | 0.4 | −0.6 | −1.3, 0.08 | 0.08 |
| Increasing Paternal Occupational Class (Lowest (Class 6) to Highest (Class 1)) a | |||||||||||||||
| Multivariable, observables b | 0.5 | 0.002, 1.0 | 0.05 | −0.001 | −0.1, 0.1 | 1.0 | 0.2 | −0.2, 0.5 | 0.3 | 0.2 | −0.6, 1.0 | 0.6 | −0.1 | −0.3, 0.06 | 0.2 |
| Multivariable, constructed scores c | 0.5 | 0.02, 1.0 | 0.04 | −0.01 | −0.1, 0.1 | 0.8 | 0.1 | −0.2, 0.4 | 0.5 | 0.3 | −0.5, 1.0 | 0.5 | −0.1 | −0.3, 0.05 | 0.2 |
| Inverse probability weighted, constructed scores d | 0.4 | −0.2, 0.9 | 0.2 | −0.04 | −0.2, 0.1 | 0.7 | −0.03 | −0.4, 0.4 | 0.9 | 0.8 | −0.3, 2.0) | 0.1 | −0.1 | −0.3, 0.01 | 0.08 |
| Increasing Maternal Education (≤8 Years, 9–12 Years, ≥13 Years) a | |||||||||||||||
| Multivariable, observables b | 0.9 | −0.2, 2.0 | 0.1 | 0.3 | 0.03, 0.6 | 0.03 | −0.2 | −1.0, 0.5 | 0.5 | 1.4 | −0.4, 3.2 | 0.1 | 0.07 | −0.3, 0.4 | 0.7 |
| Multivariable, constructed scores c | 0.6 | −0.5, 1.7 | 0.3 | 0.3 | 0.003, 0.5 | 0.05 | −0.4 | −1.1, 0.3 | 0.3 | 1.5 | −0.2, 3.1 | 0.08 | 0.1 | (−0.3, 0.5) | 0.6 |
| Inverse probability weighted, constructed scores d | 1.4 | −0.3, 3.1 | 0.1 | 0.5 | 0.1, 0.8 | 0.008 | −0.5 | −1.5, 0.5 | 0.3 | −0.04 | −2.9, 2.8 | 1.0 | 0.3 | −0.4, 0.9 | 0.4 |
| Increasing Paternal Education (≤8 Years, 9–12 Years, ≥13 Years) a | |||||||||||||||
| Multivariable, observables b | 0.8 | −0.3, 1.8 | 0.2 | 0.1 | −0.1, 0.4 | 0.3 | −0.4 | −1.1, 0.3 | 0.3 | 1.0 | −0.7, 2.7 | 0.3 | −0.3 | −0.6, 0.1 | 0.2 |
| Multivariable, constructed scores c | 0.5 | −0.5, 1.5 | 0.3 | 0.1 | −0.1, 0.3 | 0.4 | −0.5 | −1.1, 0.2 | 0.2 | 1.0 | −0.6, 2.6 | 0.2 | −0.1 | −0.5, 0.2 | 0.4 |
| Inverse probability weighted, constructed scores d | 1.7 | −0.2, 3.6 | 0.07 | 0.2 | −0.2, 0.7 | 0.3 | −0.7 | −1.7, 0.4 | 0.2 | 1.6 | −1.8, 4.9 | 0.4 | 0.3 | −0.4, 1.0 | 0.4 |
Abbreviations: ABCA1 , adenosine triphosphate binding cassette subfamily A member 1 gene; CI, confidence interval; HSD11B2, hydroxysteroid (11-β) dehydrogenase 2 gene; INS-IGF2 , insulin–insulin-like growth factor 2 readthrough gene region; LEP , leptin gene; NR3C1 , nuclear receptor subfamily 3 group C member 1 (“glucocorticoid receptor”) gene.
a Adjusted for maternal prenatal characteristics (age at delivery, Western origin, any maternal smoking during pregnancy, parity, and prepregnancy overweight), daughter's perinatal characteristics (birth weight category), and daughter's life-course mediators (age at blood draw, years of completed education, marital status, religiosity, number of children, and frequency of alcohol and cigarette use) as continuous or binary variables.
b β coefficients represent percentage-point difference in methylation per unit of exposure. Two-tailed P values are given (H 0 : β = 0).
c Adjusted for prenatal maternal characteristics (age at delivery, Western origin, any maternal smoking during pregnancy, parity, and prepregnancy overweight), daughter's birth weight category, and daughter's age at blood draw as continuous or binary variables. To parallel the marginal structural model, the daughter's life-course mediators were adjusted for as dichotomized variables: adolescent overweight (self-report), “high” traditional family role (higher than median factor score base on fewer years of completed education, married status, greater religiosity, and greater number of children), and any alcohol or cigarette use (yes to either).
d Marginal structural model estimate for the controlled direct effect of higher early life socioeconomic position by each measure (i.e., paternal occupation or parental educational level) on mean percent methylation. Adolescent overweight was controlled by weighting only, while “high” traditional family role and any alcohol or cigarette use were also included in the outcome model as adjustment variables.