Constrained instruments and their application to Mendelian randomization with pleiotropy.

ABSTRACT: In Mendelian randomization (MR), inference about causal relationship between a phenotype of interest and a response or disease outcome can be obtained by constructing instrumental variables from genetic variants. However, MR inference requires three assumptions, one of which is that the genetic variants only influence the outcome through phenotype of interest. Pleiotropy, that is, the situation in which some genetic variants affect more than one phenotype, can invalidate these genetic variants for use as instrumental variables; thus a naive analysis will give biased estimates of the causal relation. Here, we present new methods (constrained instrumental variable [CIV] methods) to construct valid instrumental variables and perform adjusted causal effect estimation when pleiotropy exists and

SUBMITTER: Jiang L 

PROVIDER: S-EPMC6537099 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature