Quality control and analytic best practices for testing genetic models of sex differences in large populations

Phenotypic sex-based differences exist for many complex traits. In other cases, phenotypes may be similar, but underlying biology may vary. Thus, sex-aware genetic analyses are becoming increasingly important for understanding the mechanisms driving these differences. To this end, we provide a guide outlining the current best practices for testing various models of sex-dependent genetic effects in complex traits and disease conditions, noting that this is an evolving field. Insights from sex-aware analyses will not only teach us about the biology of complex traits but also aid in achieving the goals of precision medicine and health equity for all. Sex-associated characteristics influence human health in many ways. This primer reviews best practices for testing various models of sex-related genetic effects in complex traits and diseases. Such analyses not only improve our understanding of biology but can also, when done properly, further precision medicine and health equity goals.