It is more difficult to imagine predictive variants accounting for a sizeable proportion of disease risk without also explaining a sizeable proportion of heritability, and the limited incremental value in disease prediction of variants identified so far suggests that genetic prediction of complex diseases on a population basis will be challenging 69–71. Still, the identification of even many hundreds of risk variants of small effect should permit identification of the small proportion of a population at the highest genetically defined risk, in which targeted prevention strategies should be explored. If testing of such variants was to be conducted across several diseases, as is now feasible with dense genome-wide association genotyping and will be greatly facilitated by whole-genome sequencing, a sizeable number of people could be identified to be at greatly increased risk for at least one disease. Identification of genetic variants that influence disease risk, prognosis, or the response to treatment should enable the development of diagnostic and interventional strategies that are safe, effective and as necessary, individualized71, although the value of genetic variants in disease prediction and the steps
