Causal Inference in Transcriptome-Wide Association Studies with Invalid Instruments and GWAS Summary Data.

ABSTRACT: Transcriptome-wide association studies (TWAS) have recently emerged as a popular tool to discover (putative) causal genes by integrating an outcome GWAS dataset with another gene expression/transcriptome GWAS (called eQTL) dataset. In our motivating and target application, we'd like to identify causal genes for low-density lipoprotein cholesterol (LDL), which is crucial for developing new treatments for hyperlipidemia and cardiovascular diseases. The statistical principle underlying TWAS is (two-sample) two-stage least squares (2SLS) using multiple correlated SNPs as instrumental variables (IVs); it is closely related to typical (two-sample) Mendelian randomization (MR) using independent SNPs as IVs, which is expected to be impractical and lower-powered for TWAS (and some other) applicatio

SUBMITTER: Xue H 

PROVIDER: S-EPMC10557939 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature