Association studies have been reported for decades but now, rather than looking at a few ‘candidate’ genes, GWA can examine SNPs systematically across the genome. Before GWA, linkage analysis, which traces co-inheritance of a DNA marker and a trait within families, was able to scan the genome with only a few hundred DNA markers but could only detect genes of large effect size. Although linkage analysis was successful in identifying genes responsible for rare single-gene disorders, linkage analyses of common disorders and complex traits generally came up empty handed in terms of replicable linkages. This finding suggested that genetic influence on common disorders and complex traits may be due to multiple genes of small effect. Association is complementary to linkage in that it can detect much smaller effect sizes if sample sizes are large. However, unlike linkage, hundreds of thousands of DNA markers are needed to conduct association analyses across the genome. Such a project was inconceivable a few years ago because genotyping 500,000 SNPs in 1000 cases and 1000 controls would have required a billion genotypings, which would cost many millions of dollars. Now with microarrays such a study would cost a few hundred thousand dollars.
