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van den Bedem, S.

Publications and source records attributed to van den Bedem, S..

2 recordsLinked to original sources

Genome-wide analysis of social behaviour in context: a meta-regression approach across social domains, reporters and developmental stages

Social behaviour is a heritable, context-dependent trait that changes across social settings and development, influencing wellbeing and mental health. We present the first genome-wide meta-regression study of social behaviour from infancy to early adulthood, leveraging 491,246 repeat measures of low prosocial behaviour and peer/social difficulties in European-ancestry cohorts (Neff=121,777, Nind=73,321). We modelled heterogeneity in genetic effects across social domains, informants, and ages (2-29 years), capturing social context through genomic influences. Six loci were identified, including variation within CADM2 (p=2.51x10-9). The SNP-based heritability was modest (2-7%), and the genetic architecture of social behaviour multidimensional. Polygenic scores demonstrated predictability and accuracy in independent European-ancestry cohorts and, partially, in African-ancestry cohorts (Nind=16,305). Genetic correlations with later-life and mental health outcomes showed context-dependent patterns. Modelling predicted onsets of associations with social behaviour revealed distinct profiles, as observed for autism, ADHD, depression and schizophrenia, highlighting novel opportunities to genetically proxy developmental trajectories.

genomics↗

Disentangling multivariate relationships between cognition, language and social traits: structures of G, E, and rGE

BackgroundCognitive, language, and social abilities are complex, heritable and intertwined traits shaping childrens development and later mental health. To better understand cross-trait interrelationships, we model here the structures of shared genomic and shared non-genomic/residual (i.e. broadly environmental) influences, and their correlation (rGE), investigating cognitive, language, and social behavioural/communication measures. MethodsData were obtained for unrelated children (8-13 years) from two population-based cohorts: the UK Avon Longitudinal Study of Parents and Children (ALSPAC, N[≤]6,543) and the US Adolescent Brain Cognitive DevelopmentSM (ABCD) Study (N[≤]4,412), and analyses were carried out implementing an extended data-driven genetic-relationship-matrix structural equation modelling (GRM-SEM) approach. ResultsIn ALSPAC, we identified two independent phenotypic domains, each captured by a structurally matching pair consisting of a genomic (A) and a non-genomic/residual (E) factor. The first domain reflected cognitive/language difficulties, with the largest genomic and residual factor loadings ({lambda}A and {lambda}E, respectively) for verbal IQ ({lambda}A=0.73(SE=0.05); {lambda}E=0.57(SE=0.07)). The second domain captured social difficulties, with the largest {lambda}A and {lambda}E for social communication measures ({lambda}A=0.39(SE=0.10); {lambda}E=0.82(SE=0.10)). We identified trait-specific rGE between pairs of A and E factors with different directions of effect (cognition/language rGE=0.89(SE=0.18), social rGE=-0.62(SE=0.17)). rGE patterns were linked to increased measurable A and E contributions for cognition/language difficulties, but decreased contributions for social problems. Analyses in ABCD confirmed the two domains for E and phenotypic structures, although genomic contributions were low. ConclusionsIn childhood, cognitive/language abilities versus social abilities are influenced by distinct genomic and/or environmental factors, potentially interlinked through trait-specific rGE, suggesting differences in developmental processes.

genomics↗