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Evidence From a Meta-analysis of Twin Studies

Patrick F. Sullivan, MD, FRANZCP; Kenneth S. Kendler, MD; Michael C. Neale, PhD

Arch Gen Psychiatry. 2003;60:1187-1192.

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.

From the Departments of Genetics and Psychiatry, University of North Carolina at Chapel Hill (Dr Sullivan); and the Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond (Drs Kendler and Neale).

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