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

• Published in: Nature communications Vol. 8; no. 1; p. 15833
• Main Authors: Mullins, Niamh, Ingason, Andrés, Porter, Heather, Euesden, Jack, Gillett, Alexandra, Ólafsson, Sigurgeir, Gudbjartsson, Daniel F., Lewis, Cathryn M., Sigurdsson, Engilbert, Saemundsen, Evald, Gudmundsson, Ólafur Ó, Frigge, Michael L., Kong, Augustine, Helgason, Agnar, Walters, G. Bragi, Gustafsson, Omar, Stefansson, Hreinn, Stefansson, Kari
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13-06-2017; Nature Publishing Group; Nature Portfolio
• Subjects: 45/43; 631/208/182; 631/208/205; 692/699/476/1373; Adult; Age; Aged; Aged, 80 and over; Attention Deficit Disorder with Hyperactivity - genetics; Attention deficit hyperactivity disorder; Autism; Autistic Disorder - genetics; Behavior disorders; Bipolar disorder; Bipolar Disorder - genetics; Children; Diseases; Disorders; Evolution; Female; Fitness; Genetic Fitness; Genetic Predisposition to Disease; Genetics, Population; Genotype; Geriatrics; Humanities and Social Sciences; Humans; Iceland; Male; Mental depression; Mental disorders; Middle Aged; multidisciplinary; Multifactorial Inheritance; Negative selection; Polymorphism, Single Nucleotide; Reproduction; Reproductive fitness; Risk; Schizophrenia; Schizophrenia - genetics; Science; Science (multidisciplinary); Iceland
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms15833

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.
Why genetic variants that confer risk for psychiatric disorders persist in the genome is an evolutionary conundrum. Here, Mullins
et al
. report association of polygenic risk for autism with having fewer children and polygenic risk for ADHD with higher reproductive fitness.