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Selection bias affects Mendelian randomization investigations when selectioninto the study sample depends on a collider between the genetic variant andconfounders of the risk factor-outcome association. However, the relativeimportance of selection bias for Mendelian randomization compared to otherpotential biases is unclear. We performed an extensive simulation study toassess the impact of selection bias on a typical Mendelian randomizationinvestigation. Selection bias had a severe impact on bias and Type 1 errorrates in our simulation study, but only when selection effects were large. Formoderate effects of the risk factor on selection, bias was generally small andType 1 error rate inflation was not considerable. The magnitude of bias wasalso affected by the strength of confounder-risk factor and confounder-outcomeassociations, the structure of the causal diagram and selection frequency. Theuse of inverse probability weighting ameliorated bias when the selection modelwas correctly specified, but increased bias when selection bias was moderateand the model was misspecified. Finally, we investigated whether selection biasmay explain a recently reported finding that lipoprotein(a) is not a causalrisk factor for cardiovascular mortality in individuals with previous coronaryheart disease.

Contextualizing selection bias in Mendelian randomization: how bad is it likely to be?