de Hoyos, L., Schlag, F., Jahagirdar, S., Corfield, E. C., Allegrini, A. G., Admiraal, D., de Zeeuw, E. L., Nolte, I. M., Llonga, N., Neumann, A., Lange, K., van den Bedem, S., Rietz, E. D., Motazedi, E., Eising, E., Ng, N., Palviainen, T., Wang, C. A., Thiering, E., Scatolin, S. de Hoyos, L., Schlag, F., Jahagirdar, S., Corfield, E. C., Allegrini, A. G., Admiraal, D., de Zeeuw, E. L., Nolte, I. M., Llonga, N., Neumann, A., Lange, K., van den Bedem, S., Rietz, E. D., Motazedi, E., Eising, E., Ng, N., 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., Seelemeyer, H., Kumar, A., Jeanne, A., Ahluwalia, T. S., Black, M. H., Buitelaar, J. K., Fisher, S. E., Heiskala, A., Hernández-Lorca, M., Jaddoe, V. W., Järvelin, M.-R., Koopowitz, S.-M., Lake, M. T., Lichtenstein, P., Llop, S., Luo, M., Malmberg, A., Marí, S., Oldehinkel, A. J., Pausova, Z., Pennell, C. E., Plomin, R., Reichborn-Kjennerud, T., Reilly, S., Rodriguez, A., Rolland, T., Ronald, A., Räikkönen, K., Shin, J., Artigas, M. S., Tate, A. E., Tiemeier, H., Verhoef, E., Vuoksimaa, E., Wake, M., Warrier, V., Ystrom, E., Bölte, S., Ecker, C., Bourgeron, T., Lahti, J., Stein, D. J., Bilbao, J. R., Bønnelykke, K., Bustamante, M., Paus, T., Middeldorp, C. M., Sunyer, J., Sebert, S., Standl, M., Whitehouse, A. J. O., Kaprio, J., Ramos-Quiroga, A., Ribases, M., Casas, M., Bosch, R., Morgan, A. T., Vrijkotte, T. G. M., Larsson, H., Cecil, C. A. M., Hartman, C. A., Boomsma, D. I., Rimfeld, K., Havdahl, A., & St Pourcain, B.(2025). Genome-wide analysis of social behaviour in context: A meta-regression approach across social domains, reporters and developmental stages. bioRxiv. doi:10.1101/2025.08.16.667148.
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.
Molz, B., Eising, E., Alagöz, G., Schijven, D., Francks, C., Gunz, P., & Fisher, S. E.
(2024). Imaging genomics reveals genetic architecture of the globular human braincase. bioRxiv. doi:10.1101/2024.03.20.585712.
Compared with our fossil ancestors and Neandertal kin, modern humans have evolved a distinctive skull shape, with a rounder braincase and more delicate face. Competing explanations for this rounder skull have either linked it to changes in brain organisation, or seen it as a by-product of gracilization (evolution of thinner and lighter skeletal anatomy). Here, we combined palaeoanthropological data from hominin fossils and imaging genomics data from living humans to gain insight into evolutionary and developmental mechanisms shaping this uniquely modern human phenotype. We analysed endocranial globularity from magnetic resonance imaging (MRI) brain scans and genetic data of more than 33,000 adults. We discovered 28 genomic loci significantly associated with endocranial globularity. There was genetic overlap with the brain’s ventricular system, white matter microstructure, and sulcal morphology, and with multivariate genetic analyses of reading/language skills, but not with general cognition. The associated genes exhibited enriched expression in the brain during prenatal development and early childhood. The connection to the ventricular system hints at a role for cerebrospinal fluid pressure in shaping the endocranium during development. Genes linked to endocranial globularity also showed enhanced expression in the cardiovascular and female reproductive systems. This finding suggests co-evolutionary pathways whereby changes impacting factors such as energy needs, pregnancy, or fertility concurrently shape the brain and its structure.Competing Interest StatementThe authors have declared no competing interest.
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