The dramatic shift to GWA research was triggered by an early GWA study which identified an association of large effect size for age-related macular degeneration (Klein, Zeiss, Chew, Tsai, Sackler et al., 2005). Although the GWA sample was very small by current standards (96 cases, 50 controls) and only 100,000 SNPs were genotyped, it identified an association with an odds ratio of 4.7 and a population attributable risk of about 50%. The frequency of the risk allele was 72% in cases and 36% in controls. The association was accepted for three related reasons: it was a huge effect, it was immediately replicated in three other independent studies, and it was in a gene (complement factor H) that made sense.
