Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies

Arch Gen Psychiatry. 2003 Dec;60(12):1187-92. doi: 10.1001/archpsyc.60.12.1187.


Context: There are many published twin studies of schizophrenia. Although these studies have been reviewed previously, to our knowledge, no review has provided quantitative summary estimates of the impact of genes and environment on liability to schizophrenia that also accounted for the different ascertainment strategies used.

Objective: To calculate meta-analytic estimates of heritability in liability and shared and individual-specific environmental effects from the pooled twin data.

Data sources: We used a structured literature search to identify all published twin studies of schizophrenia, including MEDLINE, dissertation, and books-in-print searches.

Study selection: Of the 14 identified studies, 12 met the minimal inclusion criteria of systematic ascertainment.

Data synthesis: By using a multigroup twin model, we found evidence for substantial additive genetic effects-the point estimate of heritability in liability to schizophrenia was 81% (95% confidence interval, 73%-90%). Notably, there was consistent evidence across these studies for common or shared environmental influences on liability to schizophrenia-joint estimate, 11% (95% confidence interval, 3%-19%).

Conclusions: Despite evidence of heterogeneity across studies, these meta-analytic results from 12 published twin studies of schizophrenia are consistent with a view of schizophrenia as a complex trait that results from genetic and environmental etiological influences. These results are broadly informative in that they provide no information about the specific identity of these etiological influences, but they do provide a component of a unifying empirical basis supporting the rationality of searches for underlying genetic and common environmental etiological factors.

Publication types

  • Meta-Analysis
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Diseases in Twins / genetics*
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Risk Factors
  • Schizophrenia / genetics*
  • Social Environment*
  • Statistics as Topic
  • Twin Studies as Topic