A theory-based practical solution to correct for sex-differential participation bias

Abstract

Most genomic cohorts are retrospective where the exposures and outcomes are predetermined prior to sample collection. Therefore, a spurious association between an exposure and an outcome can arise if both variables affect study participation. Such concerns were raised in previous studies questioning the representativeness of the UK Biobank. Recently, a genome-wide association study (GWAS) on biological sex found many autosomal hits and non-negligible autosomal heritability which the authors attribute to selection bias. In this study, we propose a simple and a practical method that can overcome sex-driven selection bias based on theoretical analysis and simulations.