Over 350,000 records were analyzed to identify genetic markers (SNPs) and genes related to the prevalence of GERD (gastroesophageal reflux.) 25 new loci were identified, most of which also associated with increased risk of Barrett's and/or esophageal adenocarcinoma. Three of the target genes are already GERD/EA/BE drug targets and four others are drug targets for other diseases and as such would be very interesting to investigate for potential medication repurposing for reflux, BE, or EA.

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.

An J¹, Gharahkhani P¹, Law MH¹, Ong JS¹, Han X¹, Olsen CM², Neale RE^3,4,5, Lai J⁶, Vaughan TL⁷, Gockel I⁸, Thieme R⁸, Böhmer AC^9,10, Jankowski J¹¹, Fitzgerald RC¹², Schumacher J^9,10,13, Palles C¹⁴; BEACON; 23andMe Research Team, Whiteman DC², MacGregor S¹⁵

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.

PMID: 31527586 PMCID: PMC6746768 DOI: 10.1038/s41467-019-11968-2