Evidence that duplications of 22q11.2 protect against schizophrenia

Mol Psychiatry. 2014 Jan;19(1):37-40. doi: 10.1038/mp.2013.156. Epub 2013 Nov 12.


A number of large, rare copy number variants (CNVs) are deleterious for neurodevelopmental disorders, but large, rare, protective CNVs have not been reported for such phenotypes. Here we show in a CNV analysis of 47 005 individuals, the largest CNV analysis of schizophrenia to date, that large duplications (1.5-3.0 Mb) at 22q11.2--the reciprocal of the well-known, risk-inducing deletion of this locus--are substantially less common in schizophrenia cases than in the general population (0.014% vs 0.085%, OR=0.17, P=0.00086). 22q11.2 duplications represent the first putative protective mutation for schizophrenia.

Publication types

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

MeSH terms

  • Abnormalities, Multiple / epidemiology
  • Abnormalities, Multiple / genetics*
  • Chromosome Duplication / genetics*
  • Chromosomes, Human, Pair 22 / genetics
  • DNA Copy Number Variations / genetics*
  • DiGeorge Syndrome / epidemiology
  • DiGeorge Syndrome / genetics*
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Male
  • Schizophrenia / epidemiology
  • Schizophrenia / genetics*

Supplementary concepts

  • Chromosome 22q11.2 Microduplication Syndrome

Grant support