Genetic influences on hormonal markers of chronic hypothalamic-pituitary-adrenal function in human hair.

BACKGROUND: Cortisol is the primary output of the hypothalamic-pituitary-adrenal (HPA) axis and is central to the biological stress response, with wide-ranging effects on psychiatric health. Despite well-studied biological pathways of glucocorticoid function, little attention has been paid to the role of genetic variation. Conventional salivary, urinary and serum measures are strongly influenced by diurnal variation and transient reactivity. Recently developed technology can be used to measure cortisol accumulation over several months in hair, thus indexing chronic HPA function. METHOD: In a socio-economically diverse sample of 1070 twins/multiples (ages 7.80-19.47 years) from the Texas Twin Project, we estimated effects of sex, age and socio-economic status (SES) on hair concentrations of cortisol and its inactive metabolite, cortisone, along with their interactions with genetic and environmental factors. This is the first genetic study of hair neuroendocrine concentrations and the largest twin study of neuroendocrine concentrations in any tissue type. RESULTS: Glucocorticoid concentrations increased with age for females, but not males. Genetic factors accounted for approximately half of the variation in cortisol and cortisone. Shared environmental effects dissipated over adolescence. Higher SES was related to shallower increases in cortisol with age. SES was unrelated to cortisone, and did not significantly moderate genetic effects on either cortisol or cortisone. CONCLUSIONS: Genetic factors account for sizable proportions of glucocorticoid variation across the entire age range examined, whereas shared environmental influences are modest, and only apparent at earlier ages. Chronic glucocorticoid output appears to be more consistently related to biological sex, age and genotype than to experiential factors that cluster within nuclear families.

Differences in polygenic associations with educational attainment between West and East Germany before and after reunification.

Here we examine geographical and historical differences in polygenic associations with educational attainment in East and West Germany around reunification. We test this in n = 1902 25-85-year-olds from the German SOEP-G[ene] cohort. We leverage a DNA-based measure of genetic influence, a polygenic index calculated based on a previous genome-wide association study of educational attainment in individuals living in democratic countries. We find that polygenic associations with educational attainment were significantly stronger among East, but not West, Germans after but not before reunification. Negative control analyses of a polygenic index of height with educational attainment and height indicate that this gene-by-environemt interaction is specific to the educational domain. These findings suggest that the shift from an East German state-socialist to a free-market West German system increased the importance of genetic variants previously identified as important for education.

Self-control is associated with health-relevant disparities in buccal DNA-methylation measures of biological aging in older adults.

Self-control is a personality dimension that is associated with better physical health and a longer lifespan. Here, we examined (1) whether self-control is associated with buccal and saliva DNA-methylation (DNAm) measures of biological aging quantified in children, adolescents, and adults, and (2) whether biological aging measured in buccal DNAm is associated with self-reported health. Following preregistered analyses, we computed two DNAm measures of advanced biological age (principal-component PhenoAge and GrimAge Acceleration) and a DNAm measure of pace of aging (DunedinPACE) in buccal samples from the German Socioeconomic Panel Study (SOEP-G[ene], n = 1058, age range 0-72, Mage = 42.65) and saliva samples from the Texas Twin Project (TTP, n = 1327, age range 8-20, Mage = 13.50). We found that lower self-control was associated with advanced biological age in older adults (PhenoAge Acceleration ß = - .34, [- .51, - .17], p < .001; GrimAge Acceleration ß = - .34, [- .49, - .19], p < .001), but not young adults, adolescents or children. These associations remained statistically robust even after correcting for possible confounders such as socioeconomic contexts, BMI, or genetic correlates of low self-control. Moreover, a faster pace of aging and advanced biological age measured in buccal DNAm were associated with self-reported disease (PhenoAge Acceleration: ß = .13 [.06, .19], p < .001; GrimAge Acceleration: ß = .19 [.12, .26], p < .001; DunedinPACE: ß = .09 [.02, .17], p = .01). However, effect sizes were weaker than observations in blood, suggesting that customization of DNAm aging measures to buccal and saliva tissues may be necessary. Our findings are consistent with the hypothesis that self-control is associated with health via pathways that accelerate biological aging in older adults.

Associations of socioeconomic disparities with buccal DNA-methylation measures of biological aging.

BACKGROUND: Individuals who are socioeconomically disadvantaged are at increased risk for aging-related diseases and perform less well on tests of cognitive function. The weathering hypothesis proposes that these disparities in physical and cognitive health arise from an acceleration of biological processes of aging. Theories of how life adversity is biologically embedded identify epigenetic alterations, including DNA methylation (DNAm), as a mechanistic interface between the environment and health. Consistent with the weathering hypothesis and theories of biological embedding, recently developed DNAm algorithms have revealed profiles reflective of more advanced aging and lower cognitive function among socioeconomically-at-risk groups. These DNAm algorithms were developed using blood-DNA, but social and behavioral science research commonly collect saliva or cheek-swab DNA. This discrepancy is a potential barrier to research to elucidate mechanisms through which socioeconomic disadvantage affects aging and cognition. We therefore tested if social gradients observed in blood DNAm measures could be reproduced using buccal-cell DNA obtained from cheek swabs. RESULTS: We analyzed three DNAm measures of biological aging and one DNAm measure of cognitive performance, all of which showed socioeconomic gradients in previous studies: the PhenoAge and GrimAge DNAm clocks, DunedinPACE, and Epigenetic-g. We first computed blood-buccal cross-tissue correlations in n = 21 adults (GEO111165). Cross-tissue correlations were low-to-moderate (r = .25 to r = .48). We next conducted analyses of socioeconomic gradients using buccal DNAm data from SOEP-G (n = 1128, 57% female; age mean = 42 yrs, SD = 21.56, range 0-72). Associations of socioeconomic status with DNAm measures of aging were in the expected direction, but were smaller as compared to reports from blood DNAm datasets (r = - .08 to r = - .13). CONCLUSIONS: Our findings are consistent with the hypothesis that socioeconomic disadvantage is associated with DNAm indicators of worse physical health. However, relatively low cross-tissue correlations and attenuated effect sizes for socioeconomic gradients in buccal DNAm compared with reports from analysis of blood DNAm suggest that in order to take full advantage of buccal DNA samples, DNAm algorithms customized to buccal DNAm are needed.

Self-control is associated with health-relevant disparities in buccal DNA-methylation measures of biological aging in older adults.

Self-control is a personality dimension that is associated with better physical health and a longer lifespan. Here we examined (1) whether self-control is associated with buccal and saliva DNA-methylation (DNAm) measures of biological aging quantified in children, adolescents, and adults, and (2) whether biological aging measured in buccal DNAm is associated with self-reported health. Following preregistered analyses, we computed two DNAm measures of advanced biological age (PhenoAge and GrimAge Acceleration) and a DNAm measure of pace of aging (DunedinPACE) in buccal samples from the German Socioeconomic Panel Study (SOEP-G[ene], n = 1058, age range 0-72, Mage = 42.65) and saliva samples from the Texas Twin Project (TTP, n = 1327, age range 8-20, Mage = 13.50). We found that lower self-control was associated with advanced biological age in older adults (ß =-.34), but not young adults, adolescents or children. This association was not accounted for by statistical correction for socioeconomic contexts, BMI, or genetic correlates of low self-control. Moreover, a faster pace of aging and advanced biological age measured in buccal DNAm were associated with worse self-reported health (ß =.13 to ß = .19). But, effect sizes were weaker than observations in blood, thus customization of DNAm aging measures to buccal and saliva tissues may be necessary. Our findings are consistent with the hypothesis that self-control is associated with health via pathways that accelerate biological aging in older adults.

Environmental and genetic pathways between early pubertal timing and dieting in adolescence: distinguishing between objective and subjective timing.

BACKGROUND: Early pubertal timing in girls is associated with elevated risk for dieting and eating pathology. The relative importance of biological versus socio-environmental mechanisms in explaining this association remains unclear. Moreover, these mechanisms may differ between objective measures of pubertal development and girls' subjective perceptions of their own maturation. METHOD: The sample comprised 924 sister pairs from the National Longitudinal Study of Adolescent Health. Objective pubertal timing (menarcheal age), girls' perceptions of pubertal status and timing relative to peers, dieting and disordered eating behaviors were assessed during a series of confidential in-home interviews. RESULTS: Behavioral genetic models indicated that common genetic influences accounted for the association between early menarcheal age and increased risk for dieting in adolescence. In contrast, girls' subjective perceptions of their timing relative to peers were associated with dieting through an environmental pathway. Overall, subjective and objective measures of pubertal timing accounted for 12% of the variance in dieting. CONCLUSIONS: Genetic differences in menarcheal age increase risk for dieting among adolescent girls, while girls' perceptions of their maturation represent an environmentally mediated risk.

Parental depression and offspring psychopathology: a children of twins study.

BACKGROUND: Associations between parental depression and offspring affective and disruptive disorders are well documented. Few genetically informed studies have explored the processes underlying intergenerational associations. METHOD: A semi-structured interview assessing DSM-III-R psychiatric disorders was administered to twins (n=1296) from the Australian Twin Register (ATR), their spouses (n=1046) and offspring (n=2555). We used the Children of Twins (CoT) design to delineate the extent to which intergenerational associations were consistent with a causal influence or due to genetic confounds. RESULTS: In between-family analyses, parental depression was associated significantly with offspring depression [hazard ratio (HR) 1.52, 95% confidence interval (CI) 1.20-1.93] and conduct disorder (CD; HR 2.27, CI 1.31-3.93). Survival analysis indicated that the intergenerational transmission of depression is consistent with a causal (environmental) inference, with a significant intergenerational association in offspring of discordant monozygotic (MZ) twin pairs (HR 1.39, CI 1.00-1.94). Logistic regression analysis suggested that the parental depression-offspring CD association was due to shared genetic liability in the parents and offspring. No intergenerational association was found when comparing the offspring of discordant MZ twins [odds ratio (OR) 1.41, CI 0.63-3.14], but offspring of discordant dizygotic (DZ) twins differed in their rates of CD (OR 2.53, CI 0.95-6.76). All findings remained after controlling for several measured covariates, including history of depression and CD in the twins' spouses. CONCLUSIONS: The mechanisms underlying associations between parental depression and offspring psychopathology seem to differ depending on the outcome. The results are consistent with a causal environmental role of parental depression in offspring depression whereas common genetic factors account for the association of parental depression and offspring CD.