Quantifying the extent to which index event biases influence large genetic association studies

As genetic association studies increase in size to 100,000s of individuals, subtle biases may influence conclusions. One possible bias is \"index event bias\" (IEB), also called \"collider bias\", caused by the stratification by, or enrichment for, disease status when testing associations between gene variants and a disease-associated trait. We first provided a statistical framework for quantifying IEB then identified real examples of IEB in a range of study and analytical designs. We observed evidence of biased associations for some disease alleles and genetic risk scores, even in population-based studies. For example, a genetic risk score consisting of type 2 diabetes variants was associat