Risk of schizophrenia in relatives of individuals affected by schizophrenia: A meta-analysis

A meta-analysis was conducted to estimate schizophrenia incidence in first-degree relatives (FDRs) of probands diagnosed with schizophrenia. The aim was to inform future schizophrenia research and improve accuracy of risk communication to patients. Schizophrenia risk in FDRs with 1 or 2 probands with schizophrenia was investigated by conducting a systematic review of cohort and case-control studies with the following criteria: published between 1977 and 2018; reported odds ratios (OR), relative risk (RR) or sufficient raw data to calculate OR or RR; used appropriate diagnostic criteria; and reported systematic proband recruitment and ascertainment of relatives. Studies were obtained via EMBASE and MEDLINE electronic database searches. From an initial 5755 articles, 19 met the inclusion criteria. Mean effect sizes across studies were estimated using random effects methods. Estimates for schizophrenia risk were OR = 7.69 (95% CI 5.11-11.56) for FDRs of one proband with schizophrenia compared to healthy control probands, increasing to OR = 11.11 (95% CI = 1.45-85.02) for FDRs with two probands with schizophrenia. These findings support the existing literature suggesting significant genetic liability for schizophrenia. The results can be used to educate individuals with a family history of schizophrenia about their risk.