A defect in the assignment of causation remains a reliance on observational studies. Establishing causal relationships between environmental exposures in common diseases is therefore fought with errors of confounding, reverse causation and selection bias. Using Mendelian randomization, a functional genetic variant acts as a proxy for environmental exposure helping to support or reject causal hypothesis linking environmental exposure to common diseases. In this respect use of HLA testing supports Mendelian randomization looking at cases and controls prospectively