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

Niamh Mullins; Andrés Ingason; Heather Porter; Jack Euesden; Alexandra Gillett; Sigurgeir Ólafsson; Daniel F. Gudbjartsson; Cathryn M. Lewis; Engilbert Sigurdsson; Evald Saemundsen; Ólafur Gudmundsson; Michael L. Frigge; Augustine Kong; Agnar Helgason; G. Bragi Walters; Omar Gustafsson; Hreinn Stefansson; Kari Stefansson

doi:10.1038/ncomms15833

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

Niamh Mullins, Andrés Ingason, Heather Porter, Jack Euesden, Alexandra Gillett, Sigurgeir Ólafsson, Daniel F. Gudbjartsson, Cathryn M. Lewis, Engilbert Sigurdsson, Evald Saemundsen, Ólafur Gudmundsson, Michael L. Frigge, Augustine Kong, Agnar Helgason, G. Bragi Walters, Omar Gustafsson, Hreinn Stefansson, Kari Stefansson

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Abstract

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.

Original language	English
Article number	15833
Journal	Nature Communications
Volume	8
DOIs	https://doi.org/10.1038/ncomms15833
State	Published - 13 Jun 2017
Externally published	Yes

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Mullins, N., Ingason, A., Porter, H., Euesden, J., Gillett, A., Ólafsson, S., Gudbjartsson, D. F., Lewis, C. M., Sigurdsson, E., Saemundsen, E., Gudmundsson, Ó., Frigge, M. L., Kong, A., Helgason, A., Walters, G. B., Gustafsson, O., Stefansson, H., & Stefansson, K. (2017). Reproductive fitness and genetic risk of psychiatric disorders in the general population. Nature Communications, 8, Article 15833. https://doi.org/10.1038/ncomms15833

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title = "Reproductive fitness and genetic risk of psychiatric disorders in the general population",

abstract = "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.",

author = "Niamh Mullins and Andr{\'e}s Ingason and Heather Porter and Jack Euesden and Alexandra Gillett and Sigurgeir {\'O}lafsson and Gudbjartsson, {Daniel F.} and Lewis, {Cathryn M.} and Engilbert Sigurdsson and Evald Saemundsen and {\'O}lafur Gudmundsson and Frigge, {Michael L.} and Augustine Kong and Agnar Helgason and Walters, {G. Bragi} and Omar Gustafsson and Hreinn Stefansson and Kari Stefansson",

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Mullins, N, Ingason, A, Porter, H, Euesden, J, Gillett, A, Ólafsson, S, Gudbjartsson, DF, Lewis, CM, Sigurdsson, E, Saemundsen, E, Gudmundsson, Ó, Frigge, ML, Kong, A, Helgason, A, Walters, GB, Gustafsson, O, Stefansson, H & Stefansson, K 2017, 'Reproductive fitness and genetic risk of psychiatric disorders in the general population', Nature Communications, vol. 8, 15833. https://doi.org/10.1038/ncomms15833

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AU - Mullins, Niamh

AU - Ingason, Andrés

AU - Porter, Heather

AU - Euesden, Jack

AU - Gillett, Alexandra

AU - Ólafsson, Sigurgeir

AU - Gudbjartsson, Daniel F.

AU - Lewis, Cathryn M.

AU - Sigurdsson, Engilbert

AU - Saemundsen, Evald

AU - Gudmundsson, Ólafur

AU - Frigge, Michael L.

AU - Kong, Augustine

AU - Helgason, Agnar

AU - Walters, G. Bragi

AU - Gustafsson, Omar

AU - Stefansson, Hreinn

AU - Stefansson, Kari

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AB - 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.

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

Abstract

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