Sex differences in disease genetics

Abstract

There is long-standing evidence for gene-by-sex interactions in disease risk, which can now be tested in genome-wide association studies with participant numbers in the hundreds of thousands. Contemporary methods start with a separate test for each sex, but simulations suggest a more powerful approach should be to use sex as an interaction term in a single test. The traits currently with the most compelling evidence for sex-dependent genetic effects are for adiposity (predictive of cardiac disease), type II diabetes, asthma and inflammatory bowel disease. Sexually dimorphic gene expression varies dynamically, by age, tissue type, and chromosome, so sex dependent genetic effects are expected for a wide range of diseases.