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

Genome-wide analysis of social behaviour in context: a meta-regression approach across social domains, reporters and developmental stages 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. Competing Interest Statement H.L. reports receiving grants from Shire Pharmaceuticals; personal fees from and serving as a speaker for Medice, Shire/Takeda Pharmaceuticals and Evolan Pharma AB; all outside the submitted work. H.L. is editor-in-chief of JCPP Advances. J.A.R-Q. was on the speakers bureau and/or acted as a consultant for Biogen, Idorsia, Casen-Recordati, Janssen-Cilag, Novartis, Takeda, Bial, Sincrolab, Neuraxpharm, Novartis, BMS, Medice, Rubio, Uriach, Technofarma and Raffo in the last 3 years. J.A.R-Q. also received travel awards (air tickets + hotel) for taking part in psychiatric meetings from Idorsia, Janssen-Cilag, Rubio, Takeda, Bial and Medice. The Department of Psychiatry, chaired by J.A.R-Q., received unrestricted educational and research support from the following companies in the last 3 years: Exeltis, Idorsia, Janssen-Cilag, Neuraxpharm, Oryzon, Roche, Probitas and Rubio. E.D.R. has served as a speaker for Shire Sweden AB, a Takeda Pharmaceutical Company, outside of this work. S.B. discloses that he has in the last 3 years acted as a consultant or lecturer for Medice, Takeda, and LinusBio. S.B. receives royalties for textbooks and diagnostic tools from Hogrefe, UTB, Ernst Reinhardt, Kohlhammer, and Liber. S.B. is a partner in NeuroSupportSolutions International AB. All other authors declare no conflict of interest. Funder Information Declared Subject Area - Biochemistry (17625) - Bioengineering (13852) - Bioinformatics (41825) - Biophysics (21397) - Cancer Biology (18524) - Cell Biology (25417) - Clinical Trials (138) - Developmental Biology (13350) - Ecology (19858) - Epidemiology (2067) - Evolutionary Biology (24277) - Genetics (15581) - Genomics (22459) - Immunology (17698) - Microbiology (40278) - Molecular Biology (17134) - Neuroscience (88400) - Paleontology (666) - Pathology (2823) - Pharmacology and Toxicology (4812) - Physiology (7632) - Plant Biology (15106) - Synthetic Biology (4281) - Systems Biology (9807) - Zoology (2266)