作者
Leah C Kottyan, Benjamin P Davis, Joseph D Sherrill, Kan Liu, Mark Rochman, Kenneth Kaufman, Matthew T Weirauch, Samuel Vaughn, Sara Lazaro, Andrew M Rupert, Mojtaba Kohram, Emily M Stucke, Katherine A Kemme, Albert Magnusen, Hua He, Phillip Dexheimer, Mirna Chehade, Robert A Wood, Robbie D Pesek, Brian P Vickery, David M Fleischer, Robert Lindbad, Hugh A Sampson, Vincent A Mukkada, Phil E Putnam, J Pablo Abonia, Lisa J Martin, John B Harley, Marc E Rothenberg
发表日期
2014/8
期刊
Nature genetics
卷号
46
期号
8
页码范围
895-900
出版商
Nature Publishing Group US
简介
Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder associated with allergic hypersensitivity to food. We interrogated >1.5 million genetic variants in EoE cases of European ancestry and subsequently in a multi-site cohort with local and out-of-study control subjects. In addition to replicating association of the 5q22 locus (meta-analysis P = 1.9 × 10−16), we identified an association at 2p23 spanning CAPN14 (P = 2.5 × 10−10). CAPN14 was specifically expressed in the esophagus, was dynamically upregulated as a function of disease activity and genetic haplotype and after exposure of epithelial cells to interleukin (IL)-13, and was located in an epigenetic hotspot modified by IL-13. Genes neighboring the top 208 EoE-associated sequence variants were enriched for esophageal expression, and multiple loci for allergic sensitization were associated with EoE susceptibility (4.8 × 10−2 < P < 5.1 × 10−11 …
学术搜索中的文章
LC Kottyan, BP Davis, JD Sherrill, K Liu, M Rochman… - Nature genetics, 2014