A robust and efficient method for Mendelian randomization with hundreds of genetic variants

Mendelian randomization (MR) is an epidemiological technique that uses genetic variants to distinguish correlation from causation in observational data. The reliability of a MR investigation depends on the validity of the genetic variants as instrumental variables (IVs). We develop the contamination mixture method, a method for MR with two modalities. First, it identifies groups of genetic variants with similar causal estimates, which may represent distinct mechanisms by which the risk factor influences the outcome. Second, it performs MR robustly and efficiently in the presence of invalid IVs. Compared to other robust methods, it has the lowest mean squared error across a range of realistic scenarios. The…

• W
  Wellcome

  Award: 204623/Z/16/Z
• WT
  Wellcome Trust

  Awards: 204623/Z/16/Z, 204623
• NI
  National Institute for Health and Care Research
• BH
  British Heart Foundation

  Award: RG/13/13/30194
• DO
  Department of Health and Social Care
• RS
  Royal Society

  Award: 204623/Z/16/Z
• MR
  Medical Research Council

  Awards: RG/13/13/30194, MR/L003120/1, MC_UU_00002/7, MR/L003120, MR/L003120/1
• NC
  NIHR Cambridge Biomedical Research Centre