Genetic Markers of Human Evolution Are Enriched in Schizophrenia

Biol Psychiatry. 2016 Aug 15;80(4):284-292. doi: 10.1016/j.biopsych.2015.10.009. Epub 2015 Oct 21.

Abstract

Background: Why schizophrenia has accompanied humans throughout our history despite its negative effect on fitness remains an evolutionary enigma. It is proposed that schizophrenia is a by-product of the complex evolution of the human brain and a compromise for humans' language, creative thinking, and cognitive abilities.

Methods: We analyzed recent large genome-wide association studies of schizophrenia and a range of other human phenotypes (anthropometric measures, cardiovascular disease risk factors, immune-mediated diseases) using a statistical framework that draws on polygenic architecture and ancillary information on genetic variants. We used information from the evolutionary proxy measure called the Neanderthal selective sweep (NSS) score.

Results: Gene loci associated with schizophrenia are significantly (p = 7.30 × 10(-9)) more prevalent in genomic regions that are likely to have undergone recent positive selection in humans (i.e., with a low NSS score). Variants in brain-related genes with a low NSS score confer significantly higher susceptibility than variants in other brain-related genes. The enrichment is strongest for schizophrenia, but we cannot rule out enrichment for other phenotypes. The false discovery rate conditional on the evolutionary proxy points to 27 candidate schizophrenia susceptibility loci, 12 of which are associated with schizophrenia and other psychiatric disorders or linked to brain development.

Conclusions: Our results suggest that there is a polygenic overlap between schizophrenia and NSS score, a marker of human evolution, which is in line with the hypothesis that the persistence of schizophrenia is related to the evolutionary process of becoming human.

Keywords: Evolution; GWAS; Human; Neanderthal; Polygenic; Schizophrenia.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Evolution*
  • Brain / metabolism
  • Genetic Markers / genetics*
  • Genetic Predisposition to Disease / genetics*
  • Genome-Wide Association Study
  • Humans
  • Multifactorial Inheritance / genetics
  • Polymorphism, Single Nucleotide / genetics*
  • Schizophrenia / genetics*
  • Schizophrenia / pathology

Substances

  • Genetic Markers