Potential etiologic and functional implications of genome-wide association loci for human diseases and traits

We have developed an online catalog of SNP-trait associations from published genome-wide association studies for use in investigating genomic characteristics of trait/disease-associated SNPs (TASs). Reported TASs were common median risk allele frequency 36%, interquartile range (IQR) 21%-53% and were associated with modest effect sizes median odds ratio (OR) 1.33, IQR 1.20-1.61. Among 20 genomic annotation sets, reported TASs were significantly overrepresented only in nonsynonymous sites OR = 3.9 (2.2-7.0), p = 3.5 x 10(-7) and 5kb-promoter regions OR = 2.3 (1.5-3.6), p = 3 x 10(-4) compared to SNPs randomly selected from genotyping arrays. Although 88% of TASs were intronic (45%) or intergenic (43%), TASs were not overrepresented in introns and were significantly depleted in intergenic regions OR = 0.44 (0.34-0.58), p = 2.0 x 10(-9). Only slightly more TASs than expected by chance were predicted to be in regions under positive selection OR = 1.3 (0.8-2.1), p = 0.2. This new online resource, together with bioinformatic predictions of the underlying functionality at trait/disease-associated loci, is well-suited to guide future investigations of the role of common variants in complex disease etiology.