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

Lucía de Hoyos; Fenja Schlag; Sanjeevan Jahagirdar; Elizabeth C. Corfield; Andrea G. Allegrini; Danielle Admiraal; Eveline L. de Zeeuw; Ilja Maria Nolte; Natalia Llonga; Alexander Neumann; Katherine Lange; Simone van den Bedem; Ebba Du Rietz; Ehsan Motazedi; Else Eising; Nicole Ying Ting Ng; Teemu Palviainen; Carol A. Wang; Elisabeth Thiering; Sofia Scatolin; Priyanka Choudhary; Natàlia Vilor‐Tejedor; Zhijie Liao; Silvia Alemany; Casper‐Emil Tingskov Pedersen; Nora Fernández‐Jiménez; Megan L. Campbell; Polina V Girchenko; Eli Barthome; Hanna Seelemeyer

doi:10.1101/2025.08.16.667148

GenomicsbioRxivAug 16, 2025

Preprint

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

Lucía de Hoyos iD, Fenja Schlag iD, Sanjeevan Jahagirdar iD, Elizabeth C. Corfield iD, Andrea G. Allegrini iD, Danielle Admiraal, Eveline L. de Zeeuw iD, Ilja Maria Nolte iD, Natalia Llonga iD, Alexander Neumann iD, Katherine Lange iD, Simone van den Bedem iD, Ebba Du Rietz iD, Ehsan Motazedi iD, Else Eising iD, Nicole Ying Ting Ng iD, Teemu Palviainen iD, Carol A. Wang iD, Elisabeth Thiering iD, Sofia Scatolin iD, Priyanka Choudhary iD, Natàlia Vilor‐Tejedor iD, Zhijie Liao iD, Silvia Alemany iD, Casper‐Emil Tingskov Pedersen iD, , Beaté St Pourcain iD

Abstract

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.

PDF DOI