Evaluating and implementing block jackknife resampling Mendelian randomization to mitigate bias induced by overlapping samples

Hum Mol Genet. 2022 Aug 6;ddac186. doi: 10.1093/hmg/ddac186. Online ahead of print.

Abstract

Participant overlap can induce overfitting bias into Mendelian randomization (MR) and polygenic risk score (PRS) studies. Here, we evaluated a block jackknife resampling framework for genome-wide association studies (GWAS) and PRS construction to mitigate overfitting bias in MR analyses and implemented this study design in a causal inference setting using data from the UK Biobank.