Nat Commun. 2019 Sep 16;10(1):4219. doi: 10.1038/s41467-019-11968-2.

Gastroesophageal Reflux GWAS Identifies Risk Loci That Also Associate With Subsequent Severe Esophageal Diseases

Jiyuan An  1 , Puya Gharahkhani  1 , Matthew H Law  1 , Jue-Sheng Ong  1 , Xikun Han  1 , Catherine M Olsen  2 , Rachel E Neale  3   4   5 , John Lai  6 , Tom L Vaughan  7 , Ines Gockel  8 , René Thieme  8 , Anne C Böhmer  9   10 , Janusz Jankowski  11 , Rebecca C Fitzgerald  12 , Johannes Schumacher  9   10   13 , Claire Palles  14 , BEACON; 23andMe Research Team; David C Whiteman  2 , Stuart MacGregor

PMID: 31527586 PMCID: PMC6746768

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.