Robust inference of bi-directional causal relationships in presence of correlated pleiotropy with GWAS summary data.

ABSTRACT: To infer a causal relationship between two traits, several correlation-based causal direction (CD) methods have been proposed with the use of SNPs as instrumental variables (IVs) based on GWAS summary data for the two traits; however, none of the existing CD methods can deal with SNPs with correlated pleiotropy. Alternatively, reciprocal Mendelian randomization (MR) can be applied, which however may perform poorly in the presence of (unknown) invalid IVs, especially for bi-directional causal relationships. In this paper, first, we propose a CD method that performs better than existing CD methods regardless of the presence of correlated pleiotropy. Second, along with a simple but yet effective IV screening rule, we propose applying a closely related and state-of-the-art MR method in recipro

SUBMITTER: Xue H 

PROVIDER: S-EPMC9135345 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature