The genetic architecture of schizophrenia: new mutations and emerging paradigms

Annu Rev Med. 2012;63:63-80. doi: 10.1146/annurev-med-072010-091100. Epub 2011 Oct 27.


Although a genetic component of schizophrenia has been acknowledged for a long time, the underlying architecture of the genetic risk remains a contentious issue. Early linkage and candidate association studies led to largely inconclusive results. More recently, the availability of powerful technologies, samples of sufficient sizes, and genome-wide panels of genetic markers facilitated systematic and agnostic scans throughout the genome for either common or rare disease risk variants of small or large effect size, respectively. Although the former had limited success, the role of rare genetic events, such as copy-number variants (CNVs) or rare point mutations, has become increasingly important in gene discovery for schizophrenia. Importantly, recent research building upon earlier findings of de novo recurrent CNVs at the 22q11.2 locus, has highlighted a de novo mutational paradigm as a major component of the genetic architecture of schizophrenia. Recent progress is bringing us closer to earlier intervention and new therapeutic targets.

Publication types

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

MeSH terms

  • Genetic Predisposition to Disease / epidemiology*
  • Genetic Predisposition to Disease / genetics*
  • Genetics / trends*
  • Humans
  • Risk Factors
  • Schizophrenia / epidemiology*
  • Schizophrenia / genetics*