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

作者信息

Hindorff Lucia A, Sethupathy Praveen, Junkins Heather A, Ramos Erin M, Mehta Jayashri P, Collins Francis S, Manolio Teri A

机构信息

Office of Population Genomics, Genome Technology Branch, National Human Genome Research Institute, and National Center for Biotechnology Information, National Institutes of Health, Bethesda, MD 20892, USA.

出版信息

Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9362-7. doi: 10.1073/pnas.0903103106. Epub 2009 May 27.


DOI:10.1073/pnas.0903103106
PMID:19474294
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2687147/
Abstract

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.

摘要

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本文引用的文献

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Hum Mol Genet. 2008-10-15

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