The genetic contribution to disease risk and variability in response to diet: where is the hidden heritability?

Ten years ago, it was assumed that disease risk prediction and personalised nutrition based on genetic information would now be in widespread use. However, this has not (yet) transpired. The interaction of genetic make-up, diet and health is far more complex and subtle than originally thought. With a few notable exceptions, the impact of identified common genetic variants on phenotype is relatively small and variable in their penetrance. Furthermore, the known variants account for only a fraction of what we believe to be the total genetic contribution to disease risk and heterogeneity in response to environmental change. Here, the question 'how far have we progressed and are we likely to get there' (Rimbach and Minihane, 2009) is revisited with regard to the translation of genetic knowledge into public health benefit. It is concluded that progress to date has been modest. It is hoped that recent technological developments allowing the detection of rarer variants and future use of more hypothesis-driven targeted data analysis will reveal most of the currently 'hidden' significant genetic variability.