Abstract
Abstract
Gastroesophageal reflux disease (GERD) is caused by gastric acid entering the esophagus. GERD has high prevalence and is the major risk factor for Barrett’s esophagus (BE) and esophageal adenocarcinoma (EA). We conduct a large GERD GWAS meta-analysis (80,265 cases, 305,011 controls), identifying 25 independent genome-wide significant loci for GERD. Several of the implicated genes are existing or putative drug targets. Loci discovery is greatest with a broad GERD definition (including cases defined by self-report or medication data). Further, 91% of the GERD risk-increasing alleles also increase BE and/or EA risk, greatly expanding gene discovery for these traits. Our results map genes for GERD and related traits and uncover potential new drug targets for these conditions.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry
Reference47 articles.
1. Njei, B., McCarty, T. R. & Birk, J. W. Trends in esophageal cancer survival in United States adults from 1973 to 2009: a SEER database analysis. J. Gastroenterol. Hepatol. 31, 1141–1146 (2016).
2. Wong, D. J. et al. p16(INK4a) lesions are common, early abnormalities that undergo clonal expansion in Barrett’s metaplastic epithelium. Cancer Res. 61, 8284–8289 (2001).
3. Koek, G. The role of acid and duodenal gastroesophageal reflux in symptomatic GERD. Am. J. Gastroenterol. 96, 2033–2040 (2001).
4. Delaney, J. P., Cheng, J. W., Butler, B. A. & Ritchie, W. P. Gastric ulcer and regurgitation gastritis. Gut 11, 715–719 (1970).
5. Coleman, H. G., Xie, S.-H. & Lagergren, J. The epidemiology of esophageal adenocarcinoma. Gastroenterology 154, 390–405 (2018).
Cited by
49 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献