There is no doubt that WGAS have uncovered, and will continue to uncover, interesting and previously unknown polymorphic variants with measurable significant effects on a variety of common chronic diseases. Our analysis shows, however, that as the odds ratios for common variants will mostly be small, the penetrance of these variants will be very small, even though the contribution of an individual variant to the overall inherited susceptibility of a disease, as measured by the PAR, may be relatively large (Box 1). It is the penetrance, however, that determines the possibility of applying potential preventative approaches on the basis of whether an individual is a carrier of a variant. Small ORs make it very difficult to establish the functional basis for any particular association, and so to make a convincing contribution to understanding the etiology of the disease. Thus, whereas WGAS may make a major contribution to understanding the population genetic architecture of a disease, their practical applications in terms of understanding the etiology of a disease and in targeted prevention are likely to be very limited.
