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

LA Hindorff, P Sethupathy, HA Junkins… - Proceedings of the …, 2009 - National Acad Sciences
LA Hindorff, P Sethupathy, HA Junkins, EM Ramos, JP Mehta, FS Collins, TA Manolio
Proceedings of the National Academy of Sciences, 2009National Acad Sciences
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= 3.5ื …
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 ื 10−7] and 5kb-promoter regions [OR = 2.3 (1.5−3.6), p = 3 ื 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 ื 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.
National Acad Sciences