Leveraging family data to design Mendelian randomization that is provably robust to population stratification.

ABSTRACT: Mendelian randomization (MR) has emerged as a powerful approach to leverage genetic instruments to infer causality between pairs of traits in observational studies. However, the results of such studies are susceptible to biases owing to weak instruments, as well as the confounding effects of population stratification and horizontal pleiotropy. Here, we show that family data can be leveraged to design MR tests that are provably robust to confounding from population stratification, assortative mating, and dynastic effects. We show in simulations that our approach, MR-Twin, is robust to confounding from population stratification and is not affected by weak instrument bias, whereas standard MR methods yield inflated false positive rates. We then conduct an exploratory analysis of MR-Twin and o

SUBMITTER: LaPierre N 

PROVIDER: S-EPMC10538495 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature