What is Mendelian randomization (MR)?

Mendelian randomization (MR) is a method that uses genetic variants as instrumental variables (IVs) to investigate the causal relationships between exposure risk factors and outcomes in observational studies.

Concept of MR:
In observational epidemiological studies, the associations between exposure risk factors and disease are sometimes confounded. According to Menden’s second law, the inheritance of one trait is independent of the inheritance of other traits. Therefore, the random assignment of alleles during gamete formation provides a method to reduce confounding in investigating the causality of exposure to diseases.

The basic idea is that if genetic variants result in phenotypic differences that reflect the biological effects of the exposure risk factors, which in turn affect disease risk, the different genetic variants should be linked to disease risk to the degree predicted by their impact on the phenotype.

Instrumental variables:
An IV is a variable robustly associated with the risk factor of interest and can be utilized to investigate the causal impact of that risk factor on an outcome.