Getting to GRIPS with MR-Egger: Modelling directional pleiotropy independently of allele coding.

ABSTRACT: Mendelian Randomisation Egger regression (MR-Egger) is a popular method for causal inference using single-nucleotide polymorphisms (SNPs) as instrumental variables. It allows all SNPs to have direct pleiotropic effects on the outcome, provided that those effects are independent of the effects on the exposure, known as the InSIDE assumption. However, the results of MR-Egger, and the InSIDE assumption itself, are sensitive to which allele is coded as the effect allele for each SNP. A pragmatic convention is to code the alleles with positive effects on the exposure, which has some advantages in interpretation but some statistical limitations. Here we show that if the InSIDE assumption holds under all-positive coding of the exposure effects, it cannot hold under all-positive coding of the plei

SUBMITTER: Dudbridge F 

PROVIDER: S-EPMC12753088 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature