Findings for type 2 diabetes (T2D) illustrate the importance of sample size. In late 2007, there were 11 strong candidate genes: 6 discovered by GWAS, 4 based on mechanistic hypotheses, and 1 (TCF7L2) by LD mapping of a linkage region (although TCF7L2 SNPs did not explain the linkage). (47) TCF7L2 has an overall OR of 1.37; it was detected by most (not all) studies. Other T2D loci have allelic ORs between 1.1 and 1.2, requiring from 10,000 to well over 20,000 total subjects for 80% power; each locus was missed by most single studies. For example, in the WTCCC study (2,000 cases, 3,000 controls), these 11 SNPs were ranked from 2 to 26,017 in their strength of association.(47) Zeggini et al. combined over 60,000 subjects to study T2D findings that had not quite reached genomewide significance previously; 6 SNPs (implicating eight different genes) now achieved p < 5 × 10−8, with ORs from 1.09-1.15. (48)
