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

de Hoyos, L.; Schlag, F.; Jahagirdar, S.; Corfield, E. C.; Allegrini, A. G.; Admiraal, D. A. G.; de Zeeuw, E. L.; Nolte, I. M.; Llonga, N.; Neumann, A.; Lange, K.; van den Bedem, S.; Du Rietz, E.; Motazedi, E.; Eising, E.; Ng, N. Y. T.; Palviainen, T.; Wang, C. A.; Thiering, E.; Scatolin, S.; Choudhary, P.; Vilor-Tejedor, N.; Liao, Z.; Alemany, S.; Pedersen, C.-E. T.; Fernandez-Jimenez, N.; Campbell, M. L.; Girchenko, P.; Barthome, E.; Kumar, A.; Jeanne, A.; Seelemeyer, H.; Ahluwalia, T. S.; Black, M. H.; Buitelaar, J. K.; Fisher, S. E.; Heiskala, A.; Hernandez-Lorca, M.; Jaddoe, V. W.; Järve

doi:10.1101/2025.08.16.667148

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bioRxiv · 10.1101/2025.08.16.667148

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

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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.

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de Hoyos, L., Schlag, F., Jahagirdar, S., Corfield, E. C., Allegrini, A. G., Admiraal, D. A. G., de Zeeuw, E. L., Nolte, I. M., Llonga, N., Neumann, A., Lange, K., van den Bedem, S., Du Rietz, E., Motazedi, E., Eising, E., Ng, N. Y. T., Palviainen, T., Wang, C. A., Thiering, E., Scatolin, S., Choudhary, P., Vilor-Tejedor, N., Liao, Z., Alemany, S., Pedersen, C.-E. T., Fernandez-Jimenez, N., Campbell, M. L., Girchenko, P., Barthome, E., Kumar, A., Jeanne, A., Seelemeyer, H., Ahluwalia, T. S., Black, M. H., Buitelaar, J. K., Fisher, S. E., Heiskala, A., Hernandez-Lorca, M., Jaddoe, V. W., Järve. 2025-08-17. Genome-wide analysis of social behaviour in context: a meta-regression approach across social domains, reporters and developmental stages. https://doi.org/10.1101/2025.08.16.667148

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