5. Mendelian randomization

Associations between modifiable exposures and disease seen in observational epidemiology are sometimes confounded and thus misleading, despite our best efforts to improve the design and analysis of studies. Mendelian randomization, the random assortment of genes from parents to offspring that occurs during gamete formation and conception provides one method for assessing the causal nature of some environmental exposures. The association between a disease and a polymorphism that mimics the biological link between a proposed exposure and disease is not generally susceptible to the reverse causation or confounding that may distort interpretations of conventional observational studies. This approach, which uses gene-intermediate phenotype-disease associations as a way of inferring the causal nature of associations between potentially modifiable environmental, dietary or physiological characteristics and disease [1] is an area of growing interest. Several examples where the phenotypic effects of polymorphisms are well documented and provide encouraging evidence of the explanatory power of Mendelian randomization are described below.