Unbiased causal inference with Mendelian randomization and covariate-adjusted GWAS data.
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ABSTRACT: Mendelian randomization (MR) facilitates causal inference with observational data using publicly available genome-wide association study (GWAS) results. In a GWAS, one or more heritable covariates may be adjusted for to estimate the direct effects of SNPs on a focal trait or to improve statistical power, which may introduce collider bias in SNP-trait association estimates, thus affecting downstream MR analyses. Numerical studies suggested that using covariate-adjusted GWAS summary data might introduce bias in univariable Mendelian randomization (UVMR), which can be mitigated by multivariable Mendelian randomization (MVMR). However, it remains unclear and even mysterious why/how MVMR works; a rigorous theory is needed to explain and substantiate the above empirical observation. In this pape
SUBMITTER: Wang P
PROVIDER: S-EPMC11875156 | biostudies-literature | 2025 Jan
REPOSITORIES: biostudies-literature
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