Biology subjects

Raffington, L.

Publications and source records attributed to Raffington, L..

12 recordsLinked to original sources

bioRxiv2026

Genomics of Educational Attainment Across 80 Years of Social and Political Transformation in Germany

Abrupt social and political transformations in twentieth-century Germany may have shifted how polygenic indices relate to educational outcomes across birth cohorts. Following a prespecified analysis plan, we harmonized genomic, educational, and regional data from four German studies, comprising 13,049 individuals born between 1918 and 1995. Polygenic index associations with educational attainment were robust and strengthened modestly across more recent birth cohorts, with no detectable difference between East and West Germany. Associations with intergenerational educational mobility showed no evidence of such strengthening but were stronger in the East than in the West. Polygenic indices were less predictive of educational attainment and educational mobility for women than for men, with no evidence of regional variation. We discuss the methodological limitations of polygenic indices for examining gene-environment interactions, and emphasize that evaluating whether these differences represent progress towards equal educational opportunity requires a normative framework that social science genetics alone cannot supply.

genomics↗

bioRxiv2026

Developmental Correlates of Epigenetic and Polygenic Indices of Cognition and Educational Attainment from Birth to Young Adulthood

Large-scale genomic studies have identified biomarkers of adult cognitive functioning and educational attainment, yet the developmental pathways connecting these biomarkers to adult outcomes remain unclear. Drawing on four cohorts, we examined the developmental correlates of an epigenetic index of adult cognitive function ( Epigenetic-g) alongside polygenic indices of cognition and education. Epigenetic-g and polygenic indices were uncorrelated and captured distinct variation in childrens cognitive and academic performance. Longitudinal analyses revealed that Epigenetic-g is plastic in early childhood, reaching moderate stability by adolescence, and, unlike polygenic indices, is not related to longitudinal cognitive growth. Twin models indicated that Epigenetic-g captures genetic and unique environmental variation relevant to cognitive and academic achievement that is not identified by current polygenic indices. Epigenetic indices relevant to psychological development can be generated from DNA methylation studies of adults, with most variation in these indices emerging early in life.

genomics↗

bioRxiv2025

From genetic disposition to academic achievement: The mediating role of non-cognitive skills across development

Genetic effects on academic achievement are likely to capture environmental, developmental, and psychological processes. How these processes contribute to translating genetic dispositions into observed academic achievement remains critically under-investigated. Here, we examined the role of non-cognitive skills--e.g., motivation, attitudes and self-regulation--in mediating education-associated genetic effects on academic achievement across development. Data were collected from 5,016 children enrolled in the Twins Early Development Study at ages 7, 9, 12, and 16, as well as their parents and teachers. We found that non-cognitive skills mediated polygenic score effects on academic achievement across development, and longitudinally, accounting for up to 64% of the total effects. Within-family analyses highlighted the contribution of non-cognitive skills beyond genetic, environmental and demographic factors that are shared between siblings, accounting for up to 83% of the total mediation effect, likely reflecting evocative/active gene-environment correlation. Our results underscore the role of non-cognitive skills in academic development in how children evoke and select experiences that align with their genetic propensity.

genomics↗

bioRxiv2024

Linked emergence of racial disparities in mental health and epigenetic biological aging across childhood and adolescence

Marginalization due to structural racism may confer an increased risk for aging-related diseases - in part - via effects on peoples mental health. Here we leverage a prospective birth cohort study to examine whether the emergence of racial disparities in mental health and DNA-methylation measures of biological aging (i.e., DunedinPACE, GrimAge Acceleration, PhenoAge Acceleration) are linked across childhood and adolescence. We further consider to what extent racial disparities are statistically accounted for by perinatal and postnatal factors in preregistered analyses of N=4,898 participants from the Future of Families & Child Wellbeing Study, of which N=2,039 had repeated saliva DNA methylation at ages 9 and 15 years. We find that racially marginalized children had higher levels of externalizing and internalizing behaviors and diverging longitudinal internalizing slopes. Black compared to White identifying children, children living in more racially segregated neighborhoods, and racially marginalized children more affected by colorism tended to have higher age-9 levels of biological aging and more biological age acceleration over adolescence. Notably, longitudinal increases in internalizing and externalizing behavior were correlated with longitudinal increases in biological aging. While racial and ethnic disparities in mental health were largely statistically accounted for by socioeconomic variables, racial differences in biological aging were often still visible beyond covariate controls. Our findings indicate that racial disparities in mental health and biological aging are linked and emerge early in life. Programs promoting racial health equity must address the psychological and physical impacts of structural racism in children. Comprehensive measures of racism are lacking in current population cohorts.

genomics↗

bioRxiv2024

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. One Sentence SummaryWe find that polygenic associations with educational attainment were significantly stronger among East, but not West, Germans after but not before reunification.

genetics↗

bioRxiv2023

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

Background and ObjectivesMethylation 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. MethodWe 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 childrens aging-related MPSs. ResultsAll 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. ConclusionsAging-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. Article SummaryMethylation profiles of biological aging are less stable in childhood than has been previously observed in adulthood. Whats Known on This SubjectMethylation profile scores (MPSs) index biological aging in adults and are cross-sectionally associated with social determinants of health in childhood. Aging-related MPSs in adulthood show very high test-retest stability but data on longitudinal stability of MPSs in childhood is sparse. What This Study AddsChildrens methylation profiles of biological aging are moderately stable across an approximately four-year period. Methylation profiles are less stable in childhood than in adulthood, suggesting that aging-related biology in childhood might be more responsive to environmental changes than in adulthood.

developmental biology↗

bioRxiv2023

Longitudinal Changes in Value-based Learning in Middle Childhood: Distinct Contributions of Hippocampus and Striatum

The hippocampal-dependent memory system and striatal-dependent memory system modulate reinforcement learning depending on feedback timing in adults, but their contributions during development remain unclear. In a 2-year longitudinal study, 6-to-7-year-old children performed a reinforcement learning task in which they received feedback immediately or with a short delay following their response. Childrens learning was found to be sensitive to feedback timing modulations in their reaction time and inverse temperature parameter, which quantifies value-guided decision-making. They showed longitudinal improvements towards more optimal value-based learning, and their hippocampal volume showed protracted maturation. Better delayed model-derived learning covaried with larger hippocampal volume longitudinally, in line with the adult literature. In contrast, a larger striatal volume in children was associated with both better immediate and delayed model-derived learning longitudinally. These findings show, for the first time, an early hippocampal contribution to the dynamic development of reinforcement learning in middle childhood, with neurally less differentiated and more cooperative memory systems than in adults.

neuroscience↗

bioRxiv2023

Genetic contributions of noncognitive skills to academic development

Noncognitive skills such as motivation and self-regulation, are partly heritable and predict academic achievement beyond cognitive skills. However, how the relationship between noncognitive skills and academic achievement changes over development is unclear. The current study examined how cognitive and noncognitive skills contribute to academic achievement from ages 7 to 16 in a sample of over 10,000 children from England and Wales. Noncognitive skills were increasingly predictive of academic achievement across development. Twin and polygenic scores analyses found that the contribution of noncognitive genetics to academic achievement became stronger over the school years. Results from within-family analyses indicated that associations with noncognitive genetics could not simply be attributed to confounding by environmental differences between nuclear families and are consistent with a possible role for evocative/active gene-environment correlations. By studying genetic effects through a developmental lens, we provide novel insights into the role of noncognitive skills in academic development.

genetics↗

bioRxiv2023

Measuring the long arm of childhood in real-time: Epigenetic predictors of BMI and social determinants of health across childhood and adolescence

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. Epigenetic mechanisms may regulate the influence of early life conditions on later life health. Recent epigenetic studies of adult blood samples have identified DNA-methylation sites associated with higher BMI and worse health (epigenetic-BMI). Here, we used longitudinal and twin study designs to examine whether epigenetic predictors of BMI developed in adults are valid biomarkers of child BMI and are sensitive to early life social determinants of health. Salivary epigenetic-BMI was calculated from two samples: (1) N=1,183 8-to-19-year-olds (609 female, mean age=13.4) from the Texas Twin Project (TTP), and (2) N=2,020 children (1,011 female) measured at 9 and 15 years from the Future of Families and Child Well-Being Study (FFCWS). We found that salivary epigenetic-BMI is robustly associated with childrens BMI (r=0.36 to r=0.50). Longitudinal analysis suggested that epigenetic-BMI is highly stable across adolescence, but remains both a leading and lagging indicator of BMI change. Twin analyses showed that epigenetic-BMI captures differences in BMI between monozygotic twins. Moreover, children from more disadvantaged socioeconomic status (SES) and marginalized race/ethnic groups had higher epigenetic-BMI, even when controlling for concurrent BMI, pubertal development, and tobacco exposure. SES at birth relative to concurrent SES best predicted epigenetic-BMI in childhood and adolescence. We show for the first time that epigenetic predictors of BMI calculated from pediatric saliva samples are valid biomarkers of childhood BMI that are sensitive to social inequalities. Our 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 have important implications for the development of early-life interventions that could significantly extend healthy life span.

genomics↗

bioRxiv2022

Associations of Socioeconomic Disparities With Buccal DNA-Methylation Measures Of Biological Aging

BackgroundIndividuals 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. ResultsWe 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 across (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). ConclusionsOur findings are consistent with the hypothesis that socioeconomic disadvantage is associated with DNAm indicators of worse physical and cognitive 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.

developmental biology↗

bioRxiv2021

Longitudinal developmental trajectories do not follow cross-sectional age associations in hippocampal subfield and memory development

Many cross-sectional findings suggest that volumes of specific hippocampal subfields increase in middle childhood and early adolescence. In contrast, a small number of available longitudinal studies observed decreased volumes in most subfields over this age range. Further, it remains unknown whether structural changes in development are associated with corresponding gains in childrens memory. Here we report cross-sectional age differences in childrens hippocampal subfield volumes together with longitudinal developmental trajectories and their relationships with memory performance. In two waves, 109 healthy participants aged 6 to 10 years (wave 1: MAge=7.25, wave 2: MAge=9.27) underwent high-resolution magnetic resonance imaging to assess hippocampal subfield volumes, and completed cognitive tasks assessing hippocampus dependent memory processes. We found that cross-sectional age-associations and longitudinal developmental trends in hippocampal subfield volumes were highly discrepant, both by subfields and in direction. Further, volumetric changes were largely unrelated to changes in memory, with the exception that increase in subiculum volume was associated with gains in spatial memory. Importantly, the observed longitudinal patterns of brain-cognition coupling could not be inferred from cross-sectional findings. We discuss potential sources of these discrepancies. This study underscores that childrens structural brain development and its relationship to cognition cannot be inferred from cross-sectional age comparisons. HighlightsO_LIThe subiculum undergoes volumetric increase between 6-10 years of age C_LIO_LIChange across two years in CA1-2 and DG-CA3 was not observed in this age window C_LIO_LIChange across two years did not reflect age differences spanning two years C_LIO_LICross-sectional and longitudinal slopes in stark contrast for hippocampal subfields C_LIO_LILongitudinal brain-cognition coupling cannot be inferred from cross-sectional data C_LI

neuroscience↗

bioRxiv2019

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

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- to 14-year-old children from the population-based Texas Twin Project, we measured cortisol output at three different time-scales: (1) diurnal fluctuation in salivary cortisol (n = 400), (2) salivary cortisol reactivity and recovery after exposure to the Trier Social Stress Test (n = 444), and (3) and cortisol concentration in hair (n = 1,210). These measures converged on two moderately correlated, yet distinguishable, dimensions of HPA function. We then 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.

physiology↗