Non-linear Mendelian randomization: detection of biases using negative controls with a focus on BMI, Vitamin D and LDL cholesterol.

ABSTRACT: Mendelian randomisation (MR) is an established technique in epidemiological investigation, using the principle of random allocation of genetic variants at conception to estimate the causal linear effect of an exposure on an outcome. Extensions to this technique include non-linear approaches that allow for differential effects of the exposure on the outcome depending on the level of the exposure. A widely used non-linear method is the residual approach, which estimates the causal effect within different strata of the non-genetically predicted exposure (i.e. the "residual" exposure). These "local" causal estimates are then used to make inferences about non-linear effects. Recent work has identified that this method can lead to estimates that are seriously biased, and a new method-the doubly-

SUBMITTER: Hamilton FW 

PROVIDER: S-EPMC11219394 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature