Genome-wide analysis of social behaviour across social domains, reporters and developmental stages: a meta-regression approach
Abstract
Abstract Social behaviour is a heritable trait linked to well-being and mental health, yet it varies across social context, including social domains, informants and development, which may shape its underlying genomic architecture. Here, we conducted a genome-wide meta-regression meta-analysis of social behaviour from infancy to early adulthood, studying ~500,000 repeated measures in European-ancestry cohorts ( N = 73,321). We modelled heterogeneity in single-variant associations across social domains (low prosocial behaviour and peer/social difficulties), multiple informants (parents, teachers and self-reports) and ages (2–29 years), identifying 6 associated loci, including variation within CADM2 ( P = 2.51 × 10 −9 ). Single nucleotide polymorphism-based heritability ranged from 2% to 7%, and the genetic architecture comprised 4 factors reflecting differences in either social domains or informants. Polygenic scores ( N = 16,305) accurately predicted contextual variation in independent cohorts, with some cross-ancestry transferability. Context-specific patterns of genetic correlations, particularly when estimating the developmental onset of associations, offer opportunities to disentangle shared trajectories linking social behaviour with later-life and mental health outcomes.
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Authors: L. de Hoyos, F. Schlag, S. Jahagirdar, E. Corfield, A. Allegrini, D. Admiraal, E. de Zeeuw, I. Nolte, N. Llonga, A. Neumann, K. Lange, S. van den Bedem, E. Rietz, E. Motazedi, E. Eising, Nicole Ying Ting Ng, T. Palviainen, C Wang, E. Thiering, S. Scatolin, P. Choudhary, N. Vilor-Tejedor, Z. Liao, S. Alemany, C. Pedersen, N. Fernandez-Jimenez, M. Campbell, P. Girchenko, E. Barthome, L. Caitlin Martin, Hanna Seelemeyer, Afsheen Kumar, Aimée Jeanne, Tarunveer S. Ahluwalia, Melissa H. Black, Jan K. Buitelaar, Simon E. Fisher, Anni Heiskala, María Hernández‐Lorca, Vincent W. V. Jaddoe, Marjo‐Riitta Järvelin, Sheri‐Michelle Koopowitz, Marilyn T. Lake, Paul Lichtenstein, Sabrina Llop, Mannan Luo, Anni Malmberg, Sergi Marí, Albertine J. Oldehinkel, Zdenka Pausová, Craig Edward Pennell, Robert J. Plomin, Ted Reichborn‐Kjennerud, Sheena Reilly, Alina Rodriguez, Thomas Rolland, Angelica Ronald, Katri Räikkönen, Jean Shin, María Soler Artigas, Ashley Tate, Henning W. Tiemeier, Ellen Verhoef, Eero Vuoksimaa, Melissa A Wake, Varun Warrier, Eivind Ystrøm, Sven Bölte, Christine Ecker, Thomas Bourgeron, Jari M. T. Lahti, Dan J. Stein, José Ramón Bilbao, Klaus Bønnelykke, Mariona Bustamante, Tomáš Paus, Christel Maria Middeldorp, Jordi Sunyer, Sylvain P Sebert, Marie Standl, Andrew Whitehouse, Jaakko A. Kaprio, Josep Antoni Ramos‐Quiroga, Marta Ribasés, Miguel Casas, Rosa Bosch, Angela Tamsin Morgan, Tanja G. M. Vrijkotte, Henrik Larsson, Charlotte A. M. Cecil, Catharina Annette Hartman, Dorret Irene Boomsma, Kaili Rimfeld, Alexandra Havdahl, Beaté St Pourcain
Institutions: The University of Queensland, Karolinska Institutet, University Medical Center Groningen, University of Groningen, Université de Montréal, Imperial College London, The University of Melbourne, Harvard University, Vrije Universiteit Amsterdam, University of Bristol, University of Helsinki, Amsterdam University Medical Centers, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana, Universitat de València, La Trobe University, University College London, Ludwig-Maximilians-Universität München, University of Copenhagen, University of the Basque Country, National University of Singapore, Universitat Autònoma de Barcelona, Barcelona Institute for Global Health, Curtin University, Radboud University Nijmegen, University of Amsterdam, Université Paris Cité, University of Cambridge, Centre National de la Recherche Scientifique, The University of Western Australia, University of Cape Town, University of Surrey, Erasmus University Rotterdam, Anglia Ruskin University, Erasmus MC, University of Zurich, Centro de Investigación Biomédica en Red de Salud Mental, University of Oulu, South African Medical Research Council, Royal Children's Hospital, University of Oslo, Universitat Jaume I, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Hunter Medical Research Institute, Universitat de Barcelona, Althaia, Goethe University Frankfurt, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institut de Recerca, University of Newcastle Australia, Centre Hospitalier Universitaire Sainte-Justine, The Kids Research Institute Australia, Griffith University, Universitat Pompeu Fabra, Hospital Del Mar, Murdoch Children's Research Institute, University Hospital Frankfurt, King's College London, Norwegian Institute of Public Health, Radboud University Medical Center, LMU Klinikum, Oulu University Hospital, Stockholm Health Care Services, Örebro University, Institut Pasteur, Melbourne Health, Gentofte Hospital, BioCruces Health research Institute, Steno Diabetes Centers, Glostrup Hospital, Helmholtz Munich, Brunel University of London, Royal Holloway University of London, Agency for Science, Technology and Research, Fundació Salut i Envelliment UAB, German Center for Pediatric and Adolescent Rheumatology, Center for Child and Adolescent Mental Health, Eastern and Southern Norway, Arkin, Centre for Biomedical Network Research on Rare Diseases, Pasqual Maragall Foundation, Lovisenberg Diakonale Høgskole, Centre for Genomic Regulation, Roskilde University, Hospital Sant Joan de Déu Barcelona, Institute for Molecular Medicine Finland, Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas, Barcelona Institute of Science and Technology, Institut de Recerca Sant Joan de Déu, Centre de Recherche en Biologie cellulaire de Montpellier, Children’s Health Queensland Hospital and Health Service, Copenhagen Prospective Studies on Asthma in Childhood, Hospital del Mar Research Institute, Max Planck Institute for Psycholinguistics, Karakter, Gènes, synapses et cognition, Department of Health and Human Services, Reinier van Arkel