Biology subjects

Okbay, A.

Publications and source records attributed to Okbay, A..

14 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

Dissecting the Predictive Accuracy of Polygenic Indexes for Behavioral Phenotypes Across Genetic Ancestries

Polygenic indexes (PGIs) trained on samples of European genetic ancestries often lose substantial predictive power when applied to non-European ancestries. While this portability problem is well recognized, its manifestation in behavioral and social traits remains understudied, and the factors driving this accuracy loss warrant more comprehensive analysis. Using data from the UK Biobank and Health and Retirement Study, we conduct a systematic analysis of PGI portability for 52 health-related, behavioral, and social phenotypes. We advance prior literature by using genome-wide PGIs, assessing cross-ancestry heritability differences, and comparing the performance of PGIs based on standard versus family-based GWAS. Our findings confirm systematic reductions in PGI predictive power for non-European ancestries--with relative accuracy being lowest in African (24%), followed by East Asian (37%) and South Asian (51%) genetic ancestries. We also find that biologically proximal traits exhibit greater portability than behavioral and social traits. We show that the relative importance of factors underlying reduced portability varies across traits and ancestries: in African ancestries, linkage disequilibrium and allele frequency differences explain most of the loss (82%), compared with smaller contributions in East (34%) and South Asian (25%) ancestries. Finally, we find that family-based GWAS PGIs can modestly improve portability for select traits, such as BMI in African ancestry, suggesting that part of the portability gap may reflect population-specific confounds in standard PGIs.

genetics↗

bioRxiv2024

Preschool musicality is associated with school-age communication abilities through genes related to rhythmicity

Early-life musical engagement is an understudied but developmentally important and heritable precursor of later (social) communication and language abilities. This study aims to uncover the aetiological mechanisms linking musical to communication abilities. We derived polygenic scores (PGS) for self-reported beat synchronisation abilities (PGSrhythmicity) in children (N[≤]6,737) from the Avon Longitudinal Study of Parents and Children and tested their association with preschool musical (0.5-5 years) and school-age (social) communication and cognition-related abilities (9-12 years). We further assessed whether relationships between preschool musicality and school-age communication are shared through PGSrhythmicity, using structural equation modelling techniques. PGSrhythmicity were associated with preschool musicality (Nagelkerke-R2=0.70-0.79%), and school-age communication and cognition-related abilities (R2=0.08-0.41%), but not social communication. We identified links between preschool musicality and school-age speech-and syntax-related communication abilities as captured by known genetic influences underlying rhythmicity (shared effect {beta}=0.0065(SE=0.0021), p=0.0016), above and beyond general cognition, strengthening support for early music intervention programmes.

genetics↗

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↗

bioRxiv2021

Cohort Profile: Genetic data in the German Socio-Economic Panel Innovation Sample (Gene-SOEP)

The German Socio-Economic Panel (SOEP) serves a global research community by providing representative annual longitudinal data of private households in Germany. The sample provides a detailed life course perspective based on a rich collection of information about living conditions, socio-economic status, family relationships, personality, values, preferences, and health. We collected genetic data from 2,598 individuals in the SOEP Innovation Sample, yielding the first genotyped sample that is representative of the entire German population (Gene-SOEP). The Gene-SOEP sample is a longitudinal study that includes 107 full-sibling pairs, 501 parent-offspring pairs, and 152 parent-offspring trios that are overlapping with the parent-offspring pairs. We constructed a repository of 66 polygenic indices in the Gene-SOEP sample based on results from well-powered genome-wide association studies. The Gene-SOEP data provides a valuable resource to study individual differences, inequalities, life-course development, health, and interactions between genetic predispositions and environment.

genetics↗

bioRxiv2019

Not just one p: Multivariate GWAS of psychiatric disorders and their cardinal symptoms reveal two dimensions of cross-cutting genetic liabilities

Understanding which biological pathways are specific versus general across diagnostic categories and levels of symptom severity is critical to improving nosology and treatment of psychopathology. Here, we combine transdiagnostic and dimensional approaches to genetic discovery for the first time, conducting a novel multivariate genome-wide association study (GWAS) of eight psychiatric symptoms and disorders broadly related to mood disturbance and psychosis. We identify two transdiagnostic genetic liabilities that distinguish between common forms of mood disturbance (major depressive disorder, bipolar II, and self-reported symptoms of depression, mania, and psychosis) versus rarer forms of serious mental illness (bipolar I, schizoaffective disorder, and schizophrenia). Biological annotation revealed divergent genetic architectures that differentially implicated prenatal neurodevelopment and neuronal function and regulation. These findings inform psychiatric nosology and biological models of psychopathology, as they suggest the severity of mood and psychotic symptoms present in serious mental illness may reflect a difference in kind, rather than merely in degree.

genetics↗

bioRxiv2018

Genomic analysis of diet composition finds novel loci and associations with health and lifestyle

We conducted genome-wide association study (GWAS) meta-analyses of relative caloric intake from fat, protein, carbohydrates and sugar in over 235,000 individuals. We identified 21 approximately independent lead SNPs. Relative protein intake exhibits the strongest relationships with poor health, including positive genetic associations with obesity, type 2 diabetes, and heart disease (rg {approx} 0.15 - 0.5). Relative carbohydrate and sugar intake have negative genetic correlations with waist circumference, waist-hip ratio, and neighborhood poverty (|rg| {approx} 0.1 - 0.3). Overall, our results show that the relative intake of each macronutrient has a distinct genetic architecture and pattern of genetic correlations suggestive of health implications beyond caloric content.

genetics↗

bioRxiv2018

Disentangling genetic overlap between Attention-Deficit/Hyperactivity Disorder, literacy and language

Interpreting polygenic overlap between ADHD and both literacy- and language-related impairments is challenging as genetic confounding can bias associations. Here, we investigate evidence for links between polygenic ADHD risk and multiple literacy- and language-related abilities (LRAs), assessed in UK children (N[≤]5,919), conditional on genetic effects shared with educational attainment (EA). Genome-wide summary statistics on clinical ADHD and years-of-schooling were obtained from large consortia (N[≤]326,041). ADHD-polygenic scores (ADHD-PGS) were inversely associated with LRAs in ALSPAC, most consistently with reading-related abilities, and explained [≤]1.6% phenotypic variation. Polygenic links were then dissected into both genetic effects shared with and independent of EA using multivariable regressions (MVR), analogous to Mendelian Randomization approaches accounting for mediating effects. Conditional on EA, polygenic ADHD risk remained associated with multiple literacy-related skills, phonemic awareness and verbal intelligence, but not language-related skills such as listening comprehension and non-word repetition. Pooled reading performance showed the strongest overlap with ADHD independent of EA. Using conservative ADHD-instruments (P-threshold<5x10-8) this corresponded to a 0.35 decrease in Z-scores per log-odds in ADHD-liability (P=9.2x10-5). Using subthreshold ADHD-instruments (P-threshold<0.0015), these associations had lower magnitude, but higher predictive accuracy, with a 0.03 decrease in Z-scores (P=1.4x10-6). Polygenic ADHD-effects shared with EA were of equal strength and at least equal magnitude compared to those independent of EA, for all LRAs studied, and only detectable using subthreshold instruments. Thus, ADHD-related polygenic links are highly susceptible to genetic confounding, concealing an ADHD-specific association profile that primarily involves reading-related impairments, but few language-related problems.

genetics↗

bioRxiv2018

Genome-wide study identifies 611 loci associated with risk tolerance and risky behaviors

Humans vary substantially in their willingness to take risks. In a combined sample of over one million individuals, we conducted genome-wide association studies (GWAS) of general risk tolerance, adventurousness, and risky behaviors in the driving, drinking, smoking, and sexual domains. We identified 611 approximately independent genetic loci associated with at least one of our phenotypes, including 124 with general risk tolerance. We report evidence of substantial shared genetic influences across general risk tolerance and risky behaviors: 72 of the 124 general risk tolerance loci contain a lead SNP for at least one of our other GWAS, and general risk tolerance is moderately to strongly genetically correlated ([Formula] to 0.50) with a range of risky behaviors. Bioinformatics analyses imply that genes near general-risk-tolerance-associated SNPs are highly expressed in brain tissues and point to a role for glutamatergic and GABAergic neurotransmission. We find no evidence of enrichment for genes previously hypothesized to relate to risk tolerance.

genetics↗

bioRxiv2017

MTAG: Multi-Trait Analysis of GWAS

We introduce Multi-Trait Analysis of GWAS (MTAG), a method for joint analysis of summary statistics from GWASs of different traits, possibly from overlapping samples. We apply MTAG to summary statistics for depressive symptoms (Neff = 354,862), neuroticism (N = 168,105), and subjective well-being (N = 388,538). Compared to 32, 9, and 13 genome-wide significant loci in the single-trait GWASs (most of which are themselves novel), MTAG increases the number of loci to 64, 37, and 49, respectively. Moreover, association statistics from MTAG yield more informative bioinformatics analyses and increase variance explained by polygenic scores by approximately 25%, matching theoretical expectations.

genomics↗

bioRxiv2017

Genetics of educational attainment aid in identifying biological subcategories of schizophrenia

Higher educational attainment (EA) is negatively associated with schizophrenia (SZ). However, recent studies found a positive genetic correlation between EA and SZ. We investigated possible causes of this counterintuitive finding using genome-wide association study results for EA and SZ (N = 443,581) and a replication cohort (1,169 controls; 1,067 cases) with deeply phenotyped SZ patients. We found strong genetic dependence between EA and SZ that cannot be explained by chance, linkage disequilibrium, or assortative mating. Instead, several genes seem to have pleiotropic effects on EA and SZ, but without a clear pattern of sign concordance. Genetic heterogeneity of SZ contributes to this finding. We demonstrate this by showing that the polygenic prediction of clinical SZ symptoms can be improved by taking the sign concordance of loci for EA and SZ into account. Furthermore, using EA as a proxy phenotype, we isolate FOXO6 and SLITRK1 as novel candidate genes for SZ.

genetics↗

bioRxiv2017

Education and coronary heart disease: a Mendelian randomization study

ObjectivesTo determine whether educational attainment is a causal risk factor in the development of coronary heart disease.\n\nDesignMendelian randomization study, where genetic data are used as proxies for education, in order to minimize confounding. A two-sample design was applied, where summary level genetic data was analysed from two publically available consortia.\n\nSettingIn the main analysis, we analysed genetic data from two large consortia (CARDIoGRAM and SSGAC), comprising of 112 cohorts from predominantly high-income countries. In addition, we also analysed genetic data from 7 additional large consortia, in order to identify putative causal mediators.\n\nParticipantsThe main analysis was of 589 377 men and women, predominantly of European origin.\n\nExposureA one standard deviation increase in the genetic predisposition towards higher education (i.e. 3.6 years of additional schooling). This was measured by 162 genetic variants that have been previously associated with education.\n\nMain outcomeCombined fatal and nonfatal coronary heart disease (63 746 events).\n\nResults3.6 years of additional education lowered the risk of coronary heart disease by a third (odds ratio = 0.67, 95% confidence interval [CI], 0.59 to 0.77, p=0.01). Equivalent increases in education were also causally associated with reductions in smoking, BMI and improvements in blood lipid profiles.\n\nConclusionsMore time spent in education is causally associated with a large reduction in the risk of coronary heart disease. This may be partly explained by changes to smoking, BMI and a blood lipids. These findings offer support for policy interventions that increase education, in order to also reduce the burden of cardiovascular disease.

epidemiology↗

bioRxiv2016

Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders

Autism spectrum disorder (ASD) risk is influenced by both common polygenic and de novo variation. The purpose of this analysis was to clarify the influence of common polygenic risk for ASDs and to identify subgroups of cases, including those with strong acting de novo variants, in which different types of polygenic risk are relevant. To do so, we extend the transmission disequilibrium approach to encompass polygenic risk scores, and introduce the polygenic transmission disequilibrium test. Using data from more than 6,400 children with ASDs and 15,000 of their family members, we show that polygenic risk for ASDs, schizophrenia, and greater educational attainment is over transmitted to children with ASDs in two independent samples, but not to their unaffected siblings. These findings hold independent of proband IQ. We find that common polygenic variation contributes additively to risk in ASD cases that carry a very strong acting de novo variant. Lastly, we find evide ...

genetics↗