Clinical Genetic Testing in Schizophrenia: A Systematic Review and Meta-Analysis

Genetic testing may provide important diagnostic information for individuals with schizophrenia, but the frequency with which clinically significant variants are identified across different testing approaches has not been systematically evaluated.

We conducted a systematic review and meta-analysis searching MEDLINE, Embase, and APA PsycINFO (January 2007-June 2023) for studies reporting results of clinical genetic testing in schizophrenia. Two independent reviewers performed abstract/title screening, full-text review, and data extraction following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A random-effects model was used to estimate the pooled and platform-specific proportions of individuals with pathogenic or likely pathogenic variants, with heterogeneity assessed using the I² statistic.

Analysis of 31 studies (20,476 participants) showed that 6% (95% CI, 4% to 7%) of individuals with schizophrenia had a clinically significant genetic variant identified. Detection rates were 6% (95% CI, 4% to 8%) for chromosomal microarray, 5% (95% CI, -0.02% to 12%) for exome sequencing, and 7% (95% CI, 2% to 12%) for genome sequencing. Substantial heterogeneity was observed across studies (I² = 95.9%). Geographic representation was limited, with no studies from Latin America, South Asia, or Africa.

Genetic testing identifies clinically informative variants in approximately 6% of individuals with schizophrenia. However, substantial heterogeneity across studies and limited geographic representation underscore the need for more standardized testing approaches and broader population sampling in future genetic research on schizophrenia.