A related issue is the use of case-control studies to examine associations with ‘secondary’ outcomes–that is, phenotypes other than the case/control outcome.29,30 In such studies, the association between genotype and secondary phenotype will be biased if both genotype and secondary phenotype are associated with case-control status. Case-control studies condition on case-control status, and thus again collider bias can bias the association between genotype and secondary phenotype. Various methods have been proposed to overcome this bias, including maximum likelihood and inverse probability weighting. This latter method requires some knowledge about the prevalence of case/control status in the intended study population, or the assumption that the disease is rare.29,30
