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

Research output: Contribution to journalReview articlepeer-review

1 Scopus citations

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.

Original languageEnglish
Pages (from-to)7-24
Number of pages18
JournalNeuron
Volume112
Issue number1
DOIs
StatePublished - 3 Jan 2024

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

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