Stability of DNA-Methylation Profiles of Biological Aging in Children and Adolescents.

Background and Objectives: Methylation profile scores (MPSs) index biological aging and aging-related disease in adults and are cross-sectionally associated with social determinants of health in childhood. MPSs thus provide an opportunity to trace how aging-related biology responds to environmental changes in early life. Information regarding the stability of MPSs in early life is currently lacking. Method: We use longitudinal data from children and adolescents ages 8-18 (N = 428, M age = 12.15 years) from the Texas Twin Project. Participants contributed two waves of salivary DNA-methylation data (mean lag = 3.94 years), which were used to construct four MPSs reflecting multi-system physiological decline and mortality risk (PhenoAgeAccel and GrimAgeAccel), pace of biological aging (DunedinPACE), and cognitive function (Epigenetic-g). Furthermore, we exploit variation among participants in whether they were exposed to the COVID-19 pandemic during the course of study participation, in order to test how a historical period characterized by environmental disruption might affect children's aging-related MPSs. Results: All MPSs showed moderate longitudinal stability (test-retest rs = 0.42, 0.44, 0.46, 0.51 for PhenoAgeAccel, GrimAgeAccel, and Epigenetic-g, and DunedinPACE, respectively). No differences in the stability of MPSs were apparent between those whose second assessment took place after the onset of the COVID-19 pandemic vs. those for whom both assessments took place prior to the pandemic. Conclusions: Aging-related DNA-methylation patterns are less stable in childhood than has been previously observed in adulthood. Further developmental research on the methylome is necessary to understand which environmental perturbations in childhood impact trajectories of biological aging and when children are most sensitive to those impacts.

Cohort profile: Genetic data in the German Socio-Economic Panel Innovation Sample (SOEP-G).

The German Socio-Economic Panel (SOEP) serves a global research community by providing representative annual longitudinal data of respondents living in private households in Germany. The dataset offers a valuable life course panorama, encompassing living conditions, socioeconomic status, familial connections, personality traits, values, preferences, health, and well-being. To amplify research opportunities further, we have extended the SOEP Innovation Sample (SOEP-IS) by collecting genetic data from 2,598 participants, yielding the first genotyped dataset for Germany based on a representative population sample (SOEP-G). The sample includes 107 full-sibling pairs, 501 parent-offspring pairs, and 152 triads, which overlap with the parent-offspring pairs. Leveraging the results from well-powered genome-wide association studies, we created a repository comprising 66 polygenic indices (PGIs) in the SOEP-G sample. We show that the PGIs for height, BMI, and educational attainment capture 22∼24%, 12∼13%, and 9% of the variance in the respective phenotypes. Using the PGIs for height and BMI, we demonstrate that the considerable increase in average height and the decrease in average BMI in more recent birth cohorts cannot be attributed to genetic shifts within the German population or to age effects alone. These findings suggest an important role of improved environmental conditions in driving these changes. Furthermore, we show that higher values in the PGIs for educational attainment and the highest math class are associated with better self-rated health, illustrating complex relationships between genetics, cognition, behavior, socio-economic status, and health. In summary, the SOEP-G data and the PGI repository we created provide a valuable resource for studying individual differences, inequalities, life-course development, health, and interactions between genetic predispositions and the environment.

Salivary Epigenetic Measures of Body Mass Index and Social Determinants of Health Across Childhood and Adolescence.

Importance: Children who are socioeconomically disadvantaged are at increased risk for high body mass index (BMI) and multiple diseases in adulthood. The developmental origins of health and disease hypothesis proposes that early life conditions affect later-life health in a manner that is only partially modifiable by later-life experiences. Objective: To examine whether epigenetic measures of BMI developed in adults are valid biomarkers of childhood BMI and if they are sensitive to early life social determinants of health. Design, Setting, and Participants: This population-based study of over 3200 children and adolescents aged 8 to 18 years included data from 2 demographically diverse US pediatric cohort studies that combine longitudinal and twin study designs. Analyses were conducted from 2021 to 2022. Exposures: Socioeconomic status, marginalized groups. Main Outcome and Measure: Salivary epigenetic BMI, BMI. Analyses were conducted to validate the use of saliva epigenetic BMI as a potential biomarker of child BMI and to examine associations between epigenetic BMI and social determinants of health. Results: Salivary epigenetic BMI was calculated from 2 cohorts: (1) 1183 individuals aged 8 to 18 years (609 female [51%]; mean age, 13.4 years) from the Texas Twin Project and (2) 2020 children (1011 female [50%]) measured at 9 years of age and 15 years of age from the Future of Families and Child Well-Being Study. Salivary epigenetic BMI was associated with children's BMI (r = 0.36; 95% CI, 0.31-0.40 to r = 0.50; 95% CI, 0.42-0.59). Longitudinal analysis found that epigenetic BMI was highly stable across adolescence but remained both a leading and lagging indicator of BMI change. Twin analyses showed that epigenetic BMI captured differences in BMI between monozygotic twins. Moreover, children from more disadvantaged socioeconomic status (b = -0.13 to -0.15 across samples) and marginalized racial and ethnic groups (b = 0.08-0.34 across samples) had higher epigenetic BMI, even when controlling for concurrent BMI, pubertal development, and tobacco exposure. Socioeconomic status at birth relative to concurrent socioeconomic status best predicted epigenetic BMI in childhood and adolescence (b = -0.15; 95% CI, -0.20 to -0.09). Conclusion and Relevance: This study demonstrated that epigenetic measures of BMI calculated from pediatric saliva samples were valid biomarkers of childhood BMI and may be associated with early-life social inequalities. The findings are in line with the hypothesis that early-life conditions are especially important factors in epigenetic regulation of later-life health. Research showing that health later in life is linked to early-life conditions has important implications for the development of early-life interventions that could significantly extend healthy life span.

Socially Stratified Epigenetic Profiles Are Associated With Cognitive Functioning in Children and Adolescents.

Children's cognitive functioning and educational performance are socially stratified. Social inequality, including classism and racism, may operate partly via epigenetic mechanisms that modulate neurocognitive development. Following preregistered analyses of data from 1,183 participants, ages 8 to 19 years, from the Texas Twin Project, we found that children growing up in more socioeconomically disadvantaged families and neighborhoods and children from marginalized racial/ethnic groups exhibit DNA methylation profiles that, in previous studies of adults, were indicative of higher chronic inflammation, lower cognitive functioning, and a faster pace of biological aging. Furthermore, children's salivary DNA methylation profiles were associated with their performance on in-laboratory tests of cognitive and academic skills, including processing speed, general executive function, perceptual reasoning, verbal comprehension, reading, and math. Given that the DNA methylation measures that we examined were originally developed in adults, our results suggest that children show molecular signatures that reflect the early life social determinants of lifelong disparities in health and cognition.

Socioeconomic Disadvantage and the Pace of Biological Aging in Children.

BACKGROUND AND OBJECTIVES: Children who grow up in socioeconomic disadvantage face increased burden of disease and disability throughout their lives. One hypothesized mechanism for this increased burden is that early-life disadvantage accelerates biological processes of aging, increasing vulnerability to subsequent disease. To evaluate this hypothesis and the potential impact of preventive interventions, measures are needed that can quantify early acceleration of biological aging in childhood. METHODS: Saliva DNA methylation and socioeconomic circumstances were measured in N = 600 children and adolescents aged 8 to 18 years (48% female) participating in the Texas Twin Project. We measured pace of biological aging using the DunedinPoAm DNA methylation algorithm, developed to quantify the pace-of-aging-related decline in system integrity. We tested if children in more disadvantaged families and neighborhoods exhibited a faster pace of aging as compared with children in more affluent contexts. RESULTS: Children living in more disadvantaged families and neighborhoods exhibited a faster DunedinPoAm-measured pace of aging (r = 0.18; P = .001 for both). Latinx-identifying children exhibited a faster DunedinPoAm-measured pace of aging compared with both White- and Latinx White-identifying children, consistent with higher levels of disadvantage in this group. Children with more advanced pubertal development, higher BMI, and more tobacco exposure exhibited faster a faster DunedinPoAm-measured pace of aging. However, DunedinPoAm-measured pace of aging associations with socioeconomic disadvantage were robust to control for these factors. CONCLUSIONS: Children growing up under conditions of socioeconomic disadvantage exhibit a faster pace of biological aging. DNA methylation pace of aging might be useful as a surrogate end point in evaluation of programs and policies to address the childhood social determinants of lifelong health disparities.

Weak and uneven associations of home, neighborhood, and school environments with stress hormone output across multiple timescales.

The progression of lifelong trajectories of socioeconomic inequalities in health and mortality begins in childhood. Dysregulation in cortisol, a stress hormone that is the primary output of the hypothalamus-pituitary-adrenal (HPA) axis, has been hypothesized to be a mechanism for how early environmental adversity compromises health. However, despite the popularity of cortisol as a biomarker for stress and adversity, little is known about whether cortisol output differs in children being raised in socioeconomically disadvantaged environments. Here, we show that there are few differences between advantaged and disadvantaged children in their cortisol output. In 8-14-year-old children from the population-based Texas Twin Project, we measured cortisol output at three different timescales: (a) diurnal fluctuation in salivary cortisol (n = 400), (b) salivary cortisol reactivity and recovery after exposure to the Trier Social Stress Test (n = 444), and (c) cortisol concentration in hair (n = 1210). These measures converged on two moderately correlated, yet distinguishable, dimensions of HPA function. We tested differences in cortisol output across nine aspects of social disadvantage at the home (e.g., family socioeconomic status), school (e.g., average levels of academic achievement), and neighborhood (e.g., concentrated poverty). Children living in neighborhoods with higher concentrated poverty had higher diurnal cortisol output, as measured in saliva; otherwise, child cortisol output was unrelated to any other aspect of social disadvantage. Overall, we find limited support for alteration in HPA axis functioning as a general mechanism for the health consequences of socioeconomic inequality in childhood.

Polygenic Scores in Developmental Psychology: Invite Genetics In, Leave Biodeterminism Behind.

Polygenic scores offer developmental psychologists new methods for integrating genetic information into research on how people change and develop across the life span. Indeed, polygenic scores have correlations with developmental outcomes that rival correlations with traditional developmental psychology variables, such as family income. Yet linking people's genetics with differences between them in socially valued developmental outcomes, such as educational attainment, has historically been used to justify acts of state-sponsored violence. In this review, we emphasize that an interdisciplinary understanding of the environmental and structural determinants of social inequality, in conjunction with a transactional developmental perspective on how people interact with their environments, is critical to interpreting associations between polygenic measures and phenotypes. While there is a risk of misuse, early applications of polygenic scores to developmental psychology have already provided novel findings that identify environmental mechanisms of life course processes that can be used to diagnose inequalities in social opportunity.

Genetic and environmental influences on pubertal hormones in human hair across development.

Puberty is a complex biopsychosocial process that can affect an array of psychiatric and medical disorders emerging in adolescence. Although the pubertal process is driven by neuroendocrine changes, few quantitative genetic studies have directly measured puberty-relevant hormones. Hair samples can now be assayed for accumulation of hormones over several months. In contrast to more conventional salivary measures, hair measures are not confounded by diurnal variation or hormonal reactivity. In an ethnically and socioeconomically diverse sample of 1286 child and adolescent twins and multiples from 672 unique families, we estimated genetic and environmental influences on hair concentrations of testosterone, DHEA, and progesterone across the period of 8-18 years of age. On average, male DHEA and testosterone were highly heritable, whereas female DHEA, progesterone, and puberty were largely influenced by environmental components. We identified sex-specific developmental windows of maximal heritability in each hormone. Peak heritability for DHEA occurred at approximately 10 years of age for males and females. Peak heritability for testosterone occurred at age 12.5 and 15.2 years for males and females, respectively. Peak heritability for male progesterone occurred at 11.2 years, while the heritability of female progesterone remained uniformly low. The identification of specific developmental windows when genetic signals for hormones are maximized has critical implications for well-informed models of hormone-behavior associations in childhood and adolescence.

Puberty, Socioeconomic Status, and Depression in Girls: Evidence for Gene × Environment Interactions.

In the current study, we tested for Gene × Environment interactions in the association between pubertal timing and adolescent depression by examining how socioeconomic factors might moderate age at menarche's relation with depressive symptoms. Participants comprised 630 female twin and sibling pairs from the National Longitudinal Study of Adolescent Health. Consistent with previous studies, results showed that genetic predispositions toward later menarche were associated with fewer depressive symptoms and that genetic predispositions toward earlier menarche were associated with more depressive symptoms. However, this pattern was subtle and evident only in girls from higher socioeconomic backgrounds. Although girls from lower socioeconomic families showed the highest overall levels of depression, their symptoms appeared unrelated to timing of physical development through either a genetic or an environmental path.

Early adverse environments and genetic influences on age at first sex: evidence for gene × environment interaction.

Youth who experience adverse environments in early life initiate sexual activity at a younger age, on average, than those from more advantaged circumstances. Evolutionary theorists have posited that ecological stress precipitates earlier reproductive and sexual onset, but it is unclear how stressful environments interact with genetic influences on age at first sex. Using a sample of 1,244 pairs of twins and non-twin full siblings from the National Longitudinal Study of Adolescent Health, the present study tested for gene-by-environment interactions (G × E) on age at first sex (AFS). Multivariate interaction models indicated that genetic influences on AFS were suppressed among low-socioeconomic-status (SES) and ethnic-minority compared with higher SES and ethnic-majority youth. Father absence did not uniquely moderate genetic influences on AFS. These results are broadly consistent with previous findings that genetic influences are minimized among individuals whose environments are characterized by elevated risk; however, future research would benefit from samples with larger numbers of individuals at the very low end of the SES spectrum.

Intellectual interest mediates gene × socioeconomic status interaction on adolescent academic achievement.

Recent studies have demonstrated that genetic influences on cognitive ability and academic achievement are larger for children raised in higher socioeconomic status (SES) homes. However, little work has been done to document the psychosocial processes that underlie this Gene × Environment interaction. One process may involve the conversion of intellectual interest into academic achievement. Analyses of data from 777 pairs of 17-year-old twins indicated that Gene × SES effects on achievement scores can be accounted for by stronger influences of genes for intellectual interest on achievement at higher levels of SES. These findings are consistent with the hypothesis that higher SES affords greater opportunity for children to seek out and benefit from learning experiences that are congruent with their genetically influenced intellectual interests.

Emergence of a Gene x socioeconomic status interaction on infant mental ability between 10 months and 2 years.

Recent research in behavioral genetics has found evidence for a Gene × Environment interaction on cognitive ability: Individual differences in cognitive ability among children raised in socioeconomically advantaged homes are primarily due to genes, whereas environmental factors are more influential for children from disadvantaged homes. We investigated the developmental origins of this interaction in a sample of 750 pairs of twins measured on the Bayley Short Form test of infant mental ability, once at age 10 months and again at age 2 years. A Gene × Environment interaction was evident on the longitudinal change in mental ability over the study period. At age 10 months, genes accounted for negligible variation in mental ability across all levels of socioeconomic status (SES). However, genetic influences emerged over the course of development, with larger genetic influences emerging for infants raised in higher-SES homes. At age 2 years, genes accounted for nearly 50% of the variation in mental ability of children raised in high-SES homes, but genes continued to account for negligible variation in mental ability of children raised in low-SES homes.