Genome-wide association studies provoke debate and a new look at strategy.

G enomewide association studies (GWAS), which began with hopes of quickly uncovering the genetic underpinnings of disease and personalizing treatment and risk prediction, are now the subject of debate in both academic journals and the general media. GWAS use microarrays to scan thousands of tissue samples from patients with a particular disease and compare the results with samples from healthy individuals, the goal being to fi nd common genetic variations associated with the disease. The problem is that the results so far have not lived up to the promise. Critics point out that although hundreds of single-nucleotide polymorphisms (SNPs) have been found to be associated with one or another disease, the magnitude of risk associated with a SNP is small in most cases. Finding them has not led to rapid drug development or a meaningful improvement in the ability to predict risk. And critics contend that continuing to spend vast amounts of money on these studies is not likely to change that picture, which refl ects the genetics and biology of complex diseases. GWAS defenders acknowledge that the approach was initially oversold with promises that it would personalize medicine in