If a disease affects men and women differently, does the disease’s mechanism differ by sex? My guess would be no. However, a recent article has me wondering. Schizophrenia symptoms, age of onset, and disease course differ in men and women, and some researchers report increased risk of schizophrenia in men relative to women. Now Shifman et al. report a single nucleotide polymorphism (SNP) associated with schizophrenia in women but not men in a recent article in PLoS Genetics.
Although schizophrenia is highly heritable, both genetic and environmental factors impact disease risk, so candidate genes have been difficult to identify. The authors analyzed 500,000 SNPs located throughout the genome. A variant of Reelin associated with increased schizophrenia risk in women but not men.
Reelin is a serine protease important in neuronal development. The identification of a Reelin variant associated with schizophrenia is consistent with previous research suggesting that schizophrenia affects neuronal development. What does its sex-specific identification say about the etiology of schizophrenia in men and women? I’m frankly a bit befuddled.