Nat Commun. 2019 Sep 16;10(1):4219. doi: 10.1038/s41467-019-11968-2.
An J1, Gharahkhani P1, Law MH1, Ong JS1, Han X1, Olsen CM2, Neale RE3,4,5, Lai J6, Vaughan TL7, Gockel I8, Thieme R8, Böhmer AC9,10, Jankowski J11, Fitzgerald RC12, Schumacher J9,10,13, Palles C14; BEACON; 23andMe Research Team, Whiteman DC2, MacGregor S15
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.