A novel two-sample Mendelian randomization framework integrating common and rare variants: application to assess the effect of HDL-C on preeclampsia risk.

ABSTRACT: Mendelian randomization (MR) has become an important technique for establishing causal relationships between risk factors and health outcomes. By using genetic variants as instrumental variables, it can mitigate bias due to confounding and reverse causation in observational studies. Current MR analyses have predominantly used common genetic variants as instruments, which represent only part of the genetic architecture of complex traits. Rare variants, which can have larger effect sizes and provide unique biological insights, have been understudied due to statistical and methodological challenges. We introduce MR-common and annotation-informed rare variants (MR-CARV), a novel framework integrating common and rare genetic variants in two-sample MR. This method leverages comprehensive genetic

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC12777983 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature