An evolutionary perspective on complex neuropsychiatric disease

Jon M McClellan; Anthony W Zoghbi; Joseph D Buxbaum; Carolina Cappi; James J Crowley; Jonathan Flint; Dorothy E Grice; Suleyman Gulsuner; Conrad Iyegbe; Sanjeev Jain; Po-Hsiu Kuo; Maria Claudia Lattig; Maria Rita Passos-Bueno; Meera Purushottam; Dan J Stein; Anna B Sunshine; Ezra S Susser; Christopher A Walsh; Olivia Wootton; Mary-Claire King

doi:10.1016/j.neuron.2023.10.037

An evolutionary perspective on complex neuropsychiatric disease

Neuron. 2024 Jan 3;112(1):7-24. doi: 10.1016/j.neuron.2023.10.037. Epub 2023 Nov 27.

Authors

Jon M McClellan¹, Anthony W Zoghbi², Joseph D Buxbaum³, Carolina Cappi³, James J Crowley⁴, Jonathan Flint⁵, Dorothy E Grice³, Suleyman Gulsuner⁶, Conrad Iyegbe⁷, Sanjeev Jain⁸, Po-Hsiu Kuo⁹, Maria Claudia Lattig¹⁰, Maria Rita Passos-Bueno¹¹, Meera Purushottam⁸, Dan J Stein¹², Anna B Sunshine¹³, Ezra S Susser¹⁴, Christopher A Walsh¹⁵, Olivia Wootton¹², Mary-Claire King¹⁶

Affiliations

¹ Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA 98195, USA.
² Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX 77030, USA.
³ Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
⁴ Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
⁵ Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁶ Department of Medicine and Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
⁷ Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
⁸ Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bengaluru 560029, India.
⁹ Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei 100, Taiwan.
¹⁰ Faculty of Sciences, University of the Andes, Bogotá, Colombia.
¹¹ Department of Genetics and Evolutionary Biology, University of São Paulo, São Paulo, Brazil.
¹² SAMRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry, University of Cape Town, Cape Town, South Africa.
¹³ Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA 98195, USA; Department of Medicine and Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
¹⁴ Department of Epidemiology, Mailman School of Public Health, and New York State Psychiatric Institute, Columbia University, New York, NY 10032, USA.
¹⁵ Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Division of Genetics and Genomics and Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA 02115, USA; Departments of Pediatrics and Neurology, Harvard Medical School, Boston, MA 02115, USA.
¹⁶ Department of Medicine and Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA. Electronic address: mcking@uw.edu.

PMID: 38016473
PMCID: PMC10842497 (available on 2025-01-03)
DOI: 10.1016/j.neuron.2023.10.037

Abstract

The forces of evolution-mutation, selection, migration, and genetic drift-shape the genetic architecture of human traits, including the genetic architecture of complex neuropsychiatric illnesses. Studying these illnesses in populations that are diverse in genetic ancestry, historical demography, and cultural history can reveal how evolutionary forces have guided adaptation over time and place. A fundamental truth of shared human biology is that an allele responsible for a disease in anyone, anywhere, reveals a gene critical to the normal biology underlying that condition in everyone, everywhere. Understanding the genetic causes of neuropsychiatric disease in the widest possible range of human populations thus yields the greatest possible range of insight into genes critical to human brain development. In this perspective, we explore some of the relationships between genes, adaptation, and history that can be illuminated by an evolutionary perspective on studies of complex neuropsychiatric disease in diverse populations.

Keywords: 22q11 deletion; OCD; assortative mating; autism; bipolar disorder; causality; clinical heterogeneity; complex neuropsychiatric disease; consanguinity; de novo mutation; evolution; genetic drift; genetics; genomics; migration; polygenic inheritance; rare alleles; schizophrenia; selection; somatic mutation.

An evolutionary perspective on complex neuropsychiatric disease

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