What are the assumptions under Mendelian randomization?

  • Relevance assumption (IV1): the instruments must be associated with the exposure risk factor. This means that the genetic variants are associated with exposure at a genome-wide significance level (i.e., 5*10^-8) and replicated in a few independent studies.
  • Exclusion restriction assumption (IV2): the only way the IVs influence the outcome is through the relevant exposure risk factor.
  • Independence assumption (IV3): the IVs must not associate with confounders.