Biology subjects

Forstner, A. J.

Publications and source records attributed to Forstner, A. J..

8 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↗

bioRxiv2026

(Epi-)Genomic Data in the German TwinLife Study: TwinSNPs and TECS Cohort Profiles

The German Twin Family Panel TwinLife is a nationwide longitudinal study of twins and their family members. Primarily focusing on the development of social inequalities over the life course, TwinLife has been collecting data since October 2014 starting with 4,096 twin families (Ntotal = 16,951 individuals). As Germanys largest twin study to date, TwinLife has been surveying four birth cohorts of monozygotic and dizygotic same-sex twin pairs (initially [~]5, 11, 17, and 23 years old) and their families for 11 years. Survey data have been collected through five biennial face-to-face interviews with four computer-assisted telephone interviews in the years between. In addition, saliva samples were collected before the COVID-19 pandemic (2018-2020), during the pandemic (2021), and after (2022-2024). In this Cohort Profile, we describe the curation and initial analyses of molecular genetic and epigenetic data from the two TwinLife satellite projects TwinSNPs and TECS. Together, these projects currently comprise 12,108 processed DNA samples from 6,450 participants, extracted from the first two saliva collections before and during the COVID-19 pandemic. We compared the subsamples with the overall TwinLife sample and provide an overview of derived polygenic scores (PGS), epigenetic clocks and other methylation profile scores (MPS). We found that PGS predicted sample attrition in TwinLife, with small but significant associations between higher PGS for educational attainment and continued participation. Epigenetic clocks derived from saliva were highly correlated with chronological age (r = .71 to r = .94) and were generally more stable over time than other MPS. PGS for epigenetic clocks were associated with the respective clock only during but not before the start of the pandemic. We discuss opportunities of combining prospectively assessed molecular (epi)genetic data in within-family designs such as TwinLife and its implications and avenues for future research.

genetics↗

bioRxiv2024

Age-Associated Genetic and Environmental Contributions to Epigenetic Aging Across Adolescence and Emerging Adulthood

BackgroundEpigenetic aging estimators commonly track chronological and biological aging, quantifying its accumulation (i.e., epigenetic age acceleration) or speed (i.e., epigenetic aging pace). Their scores reflect a combination of inherent biological programming and the impact of environmental factors, which are suggested to vary at different life stages. The transition from adolescence to adulthood is an important period in this regard, marked by an increasing and, then, stabilizing epigenetic aging variance. Whether this pattern arises from environmental influences or genetic factors is still uncertain. This study delves into understanding the genetic and environmental contributions to variance in epigenetic aging across these developmental stages. Using twin modeling, we analyzed four estimators of epigenetic aging, namely Horvath Acceleration, PedBE Acceleration, GrimAge Acceleration, and DunedinPACE, based on saliva samples collected at two timepoints approximately 2.5 years apart from 976 twins of four birth cohorts (aged about 9.5, 15.5, 21.5, and 27.5 years at first and 12, 18, 24, and 30 years at second measurement occasion). ResultsHalf to two-thirds (50-68%) of the differences in epigenetic aging were due to unique environmental factors, indicating the role of life experiences and epigenetic drift, besides measurement error. The remaining variance was explained by genetic (Horvath Acceleration: 24%; GrimAge Acceleration: 32%; DunedinPACE: 47%) and shared environmental factors (Horvath Acceleration: 26%; PedBE Acceleration: 47%). The genetic and shared environmental factors represented the primary sources of stable differences in corresponding epigenetic aging estimators over 2.5 years. Age moderation analyses revealed that the variance due to individually-unique environmental sources was smaller in younger than in older cohorts in epigenetic aging estimators trained on chronological age (Horvath Acceleration: 47% to 49%; PedBE Acceleration: 33% to 68%). The variance due to genetic contributions, in turn, potentially increased across age groups for epigenetic aging estimators trained in adult samples (Horvath Acceleration: 18% to 39%; GrimAge Acceleration: 24% to 43%; DunedinPACE: 42% to 57%). ConclusionsTransition to adulthood is a period of the increasing variance in epigenetic aging. Both environmental and genetic factors contribute to this trend. The degree of environmental and genetic contributions can be partially explained by the design of epigenetic aging estimators.

genomics↗

bioRxiv2020

"The Heidelberg Five" Personality Dimensions: Genome-wide Associations, Polygenic Risk for Neuroticism, and Psychopathology 20 Years after Assessment

The HeiDE study ( Heidelberger Langzeitstudie zu Risikofaktoren und Diagnose chronischer Erkrankungen) is a longitudinal population-based study that started in the 1990s and, at baseline, assessed an array of health-related personality questionnaires in 5 133 individuals. Five latent personality dimensions (The Heidelberg Five) were identified and interpreted as Emotional Lability (ELAB), Lack of Behavioral Control (LBCN), Type A Behavior (TYAB), Locus of Control over Disease (LOCC), and Psychoticism (PSYC). A subset of participants (n=3 268; after quality control) were genotyped on whole-genome arrays at follow-up. To further characterize The Heidelberg Five, we analyzed genomic underpinnings, their relations to the genetic basis of the Big Five trait Neuroticism, and longitudinal associations with lifetime psychiatric symptoms. SNP-based heritability was significant for ELAB (34%) and LBCN (29%). Five separate genome-wide association studies (GWAS) using factor scores on personality dimensions as phenotypes were conducted, only the phenotype PSYC yielded a genome-wide significant finding (p<5x10-8, top SNP rs138223660). Gene-based analyses identified significant findings for ELAB (Integrin Subunit Beta 5), TYAB (Coiled-coil Domain Containing 83), and PSYC (Nuclear Receptor Subfamily 1 Group H Member 4). Polygenic risk scores for Neuroticism, phenotypically related to ELAB, were associated with ELAB, but not with the remaining Heidelberg Five. Longitudinally, all personality dimensions were related to depressive symptoms at follow-up, with ELAB, LBCN, and PSYC also associated with lifetime anxiety symptoms. These results highlight the clinical importance of health-related personality traits, and identify LBCN as a heritable "executive function" personality trait.

genomics↗

bioRxiv2018

Genetic variation in the Major Histocompatibility Complex and association with depression

BackgroundThe prevalence of depression is higher in individuals suffering from autoimmune diseases, but the mechanisms underlying the observed comorbidities are unknown. Epidemiological findings point to a bi-directional relationship - that depression increases the risk of developing an autoimmune disease, and vice-versa. Shared genetic etiology is a plausible explanation for the overlap between depression and autoimmune diseases. In this study we tested whether genetic variation in the Major Histocompatibility Complex (MHC), which is associated with risk for autoimmune diseases, is also associated with risk for depression.\n\nMethodWe fine-mapped the classical MHC (chr6: 29.6-33.1 Mb), imputing 216 Human Leukocyte Antigen (HLA) alleles and four Complement Component 4 (C4) haplotypes in studies from the Psychiatric Genomics Consortium (PGC) Major Depressive Disorder (MDD) working group and the UK Biobank (UKB). In the 26 PGC-MDD studies, cases met a lifetime diagnosis of MDD, determined by a structured diagnostic interview. In the UKB, cases and controls were identified from an online mental health questionnaire. The total sample size was 45,149 depression cases and 86,698 controls. We tested for association between depression status and imputed MHC variants in each study and performed an inverse-variance weighted meta-analysis across the PGC-MDD and UKB samples, applying both a conservative region-wide significance threshold (3.9-e6) and a candidate threshold (1.6e-4).\n\nResultsNo HLA alleles or C4 haplotypes were associated with depression at the conservative threshold in the PGC, UKB or meta-analysis. HLA-B*08:01 was associated with modest protection for depression at the candidate threshold in the meta-analysis. Under the conservative threshold, 70 SNPs were detected in the UKB and 143 SNPs were detected in the meta-analysis, mirroring previous findings from highly powered GWAS of depression.\n\nDiscussionWe found no evidence that HLA alleles, which play a major role in the genetic susceptibility to autoimmune diseases, or C4 haplotypes, which are strongly associated with schizophrenia, confer risk for depression. These results indicate that autoimmune diseases and depression do not share common risk loci of moderate or large effect in the MHC.

genetics↗

bioRxiv2018

Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders

Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 individuals from 33 Andalusian BD multiplex families as well as 438 subjects from an independent, sporadic BD case-control cohort were analysed. Polygenic risk scores (PRS) for BD, schizophrenia, and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had significantly higher PRS for all three psychiatric disorders than the independent controls, suggesting a high baseline risk for several psychiatric disorders in the families. Moreover, familial BD cases showed significantly higher BD PRS than unaffected family members and sporadic BD cases. A plausible hypothesis is that, in multiplex families with a general increase in risk for psychiatric disease, BD development is attributable to a high burden of common variants that confer a specific risk for BD. The present analyses, therefore, demonstrated that common genetic risk variants for psychiatric disorders are likely to contribute to the high incidence of affective psychiatric disorders in the multiplex families. The PRS explained only part of the observed phenotypic variance and rare variants might have also contributed to disease development.

genetics↗

bioRxiv2018

Response to Therapeutic Sleep Deprivation: A Naturalistic Study of Clinical and Genetic Factors and Post-Treatment Depressive Symptom Trajectory

Research has shown that therapeutic sleep deprivation (SD) has rapid antidepressant effects in the majority of depressed patients. Investigation of factors preceding and accompanying these effects may facilitate the identification of the underlying biological mechanisms. This exploratory study aimed to examine clinical and genetic factors predicting response to SD and determine the impact of SD on illness course. Mood and tiredness during SD were also assessed via visual analogue scales (VAS). Depressed inpatients (n = 78) and healthy controls (n = 15) underwent ~36hrs of SD. Response to SD was defined as a score of [≤]2 on the Clinical Global Impression Scale for Global Improvement. Depressive symptom trajectories were evaluated for up to a month using self/expert ratings. Impact of genetic burden was calculated using polygenic risk scores for major depressive disorder. 72% of patients responded to SD. Responders and nonresponders did not differ in baseline self/expert depression symptom ratings, but mood subjectively measured by VAS scale differed. Response was associated with lower age (p = 0.007) and later age at life-time disease onset (p = 0.003). Higher genetic burden of depression was observed in non-responders than healthy controls. Up to a month post-SD, depressive symptoms decreased in both patients groups, but more in responders, in whom effects were sustained. The present findings suggest that re-examining SD with a greater focus on biological mechanisms will lead to better understanding of mechanisms of depression.

epidemiology↗