In the 10 years since the completion of the human genome project there has been tremendous scientific progress in genomics. After a brief period of promiscuous false discovery, methodological advances based on agnostic statistical approaches have yielded hundreds of confirmed associations between genes and disease.1 Rapid improvements in “next generation” sequencing mean that people will soon be able to carry their genome on a memory stick at an affordable cost. What scientists have yet been unable to provide, however, has been a compelling reason why anyone would want to do so.

Despite the high expectations for accurate forecasting of disease based on genetic information, and the marketing of direct-to-consumer genetic tests,2 it seems increasingly less likely that genes will have a major clinical effect on the prognosis of common complex diseases. The effects of single nucleotide polymorphisms (SNPs) tend to be small,3 they typically add little information to easily obtainable clinical or phenotypic information,4 and even in combination typically account for only a small proportion of heritability.5 The products of even the most reputable of the direct-to-consumer genetic testing companies (Navigenics, 23andMe, deCODE) can show marked differences in the calculated relative disease risks for individuals.6 Although the reasons common SNPs are so weakly predictive are not wholly settled, if SNPs interact complexly (with themselves or environmental factors) to cause complex diseases or if substantial variation in risk is the result of very uncommon genetic variants, then the use of SNPs to predict disease may prove statistically intractable. History underscores the large gap between statistically …