Mendelian randomization

Mendelian randomization

Mendelian randomization is a research method that uses naturally occurring genetic differences to test whether a particular factor actually causes a health outcome. The idea relies on the fact that genes are passed from parents to children in a way that is largely random, so certain genetic variants can act like a natural experiment: people with a gene that raises a trait can be compared to those without it to see if that trait increases disease risk. Researchers first identify genetic variants reliably associated with the factor of interest, then check whether those same variants are linked to the outcome. Because genes are set at conception, this approach reduces confusion from lifestyle or social factors that often bias observational studies and helps address whether the relationship is causal rather than just a correlation. Mendelian randomization matters because it can point scientists to true causes worth targeting for prevention or treatment, without waiting for long or expensive randomized trials. The method does have assumptions and limitations: the genetic variants must influence the outcome only through the factor being studied, they must be strongly associated with that factor, and population differences must be accounted for. Problems like variants affecting multiple traits or weak genetic instruments can lead to misleading results, so careful design and sensitivity analyses are important. When done well, it provides valuable evidence that complements other types of studies and helps prioritize public health actions.