Mendelian randomization is a statistical approach that uses gene variants to help establish whether a given environmental factor causes a particular health outcome, even in a purely observational study.
For example, people who are vitamin D deficient may be more likely to suffer from a bone fracture, but this merely tells us that there is an association between low vitamin D and bone fractures, not that one causes the other. People who get more vitamin D may be more likely to eat healthier foods and do more exercise, for example, and these confounding factors may be responsible for the reduced risk of bone fractures. To establish causation, it would be necessary to perform a randomized trial in which some individuals were selected at random to take more vitamin D, and the effects on bone fractures measured. However, such trials are expensive and not always practical or ethical.
Some people carry gene variants that make them predisposed to have low vitamin D levels, and this is where Mendelian randomization can be useful. Since gene variants are inherited at random from our parents, the distribution of a gene variant within a population can usually be considered to be random (though there are some exceptions to this), and can effectively serve as ‘nature’s randomized trial’. If people with gene variants predisposing them to low vitamin D suffer more fractures, this suggests that low vitamin D does cause fractures, provided we are confident that these gene variants aren’t associated with propensity for exercise, healthy eating, or any other confounding factors.