Schizophrenia risk and reproductive success: A Mendelian randomization study

Schizophrenia is a debilitating and heritable mental disorder associated with lower reproductive success. However, the prevalence of schizophrenia is stable over populations and time, resulting in an evolutionary puzzle: how is schizophrenia maintained in the population given its apparent fitness costs? One possibility is that increased genetic liability for schizophrenia, in the absence of the disorder itself, may confer some reproductive advantage. We assessed the correlation and causal effect of genetic liability for schizophrenia with number of children and age at first birth using data from the Psychiatric Genomics Consortium and UK Biobank. Linkage disequilibrium score regression showed little evidence of genetic correlation between genetic liability for schizophrenia and number of children (rg=0.002, p=0.84) or age at first birth (rg=-0.007, p=0.45). Mendelian randomization indicated no robust evidence of a causal effect of genetic liability for schizophrenia on number of children (mean difference: 0.003 increase in number of children per doubling in the natural log odds ratio of schizophrenia risk, 95% CI: -0.003 to 0.009, p=0.39) or age at first birth (-0.004 years lower age at first birth, 95% CI: -0.043 to 0.034, p=0.82). These results suggest that increased genetic liability for schizophrenia does not confer a reproductive advantage.