Reproductive fitness and genetic risk of psychiatric disorders in the general population

The persistence of common, heritable psychiatric disorders that reduce reproductive fitness is an evolutionary paradox. Here, we investigate the selection pressures on sequence variants that predispose to schizophrenia, autism, bipolar disorder, major depression and attention deficit hyperactivity disorder (ADHD) using genomic data from 150,656 Icelanders, excluding those diagnosed with these psychiatric diseases. Polygenic risk of autism and ADHD is associated with number of children. Higher polygenic risk of autism is associated with fewer children and older age at first child whereas higher polygenic risk of ADHD is associated with having more children. We find no evidence for a selective advantage of a high polygenic risk of schizophrenia or bipolar disorder. Rare copy-number variants conferring moderate to high risk of psychiatric illness are associated with having fewer children and are under stronger negative selection pressure than common sequence variants.The authors are grateful to the participants and we thank the research nurses and staff at the Krokhals recruitment centre. We also thank the staff at deCODE genetics core facilities for their important contribution to this work. The research leading to these results has received support from the European Community's Seventh Framework Programme under the Marie Curie Industry-Academia Partnership and Pathways (PsychDPC, GA 286213), the Innovative Medicines Initiative Joint Undertaking under grant agreement 115008 and in part by the National Institute for Health Research (NIHR) Biomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust and King's College London.Peer Reviewe