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Gastroesophageal reflux GWAS identifies risk loci that also associate with subsequent severe esophageal diseases

by Böhmer, Anne C. , Fitzgerald, Rebecca C. , Vaughan, Tom L. , Jankowski, Janusz , An, Jiyuan , Law, Matthew H. , Han, Xikun , Schumacher, Johannes , Thieme, René , Olsen, Catherine M. , Neale, Rachel E. , MacGregor, Stuart , Gharahkhani, Puya , Gockel, Ines , Whiteman, David C. , Ong, Jue-Sheng , Lai, John , Palles, Claire

in 38/39 / 45/43 / 631/208/205/2138 / 631/208/68 / 631/67/1504/1477 / 692/699/1503/1476/196 / Adenocarcinoma / Esophageal cancer / Esophageal diseases / Esophageal Diseases - genetics / Esophagus / Female / Gastric juice / Gastroesophageal reflux / Gastroesophageal Reflux - genetics / Genes / Genetic Loci / Genetic Predisposition to Disease / Genome-Wide Association Study / Genomes / Health risk assessment / Humanities and Social Sciences / Humans / Loci / Male / multidisciplinary / Polymorphism, Single Nucleotide / Risk analysis / Risk factors / Science / Science (multidisciplinary)

2019

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Gastroesophageal reflux GWAS identifies risk loci that also associate with subsequent severe esophageal diseases

2019

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2019

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Journal Article

Gastroesophageal reflux GWAS identifies risk loci that also associate with subsequent severe esophageal diseases

Böhmer, Anne C.,

Fitzgerald, Rebecca C.,

Vaughan, Tom L.,

Jankowski, Janusz,

An, Jiyuan,

Law, Matthew H.,

Han, Xikun,

Schumacher, Johannes,

Thieme, René,

Olsen, Catherine M.,

Neale, Rachel E.,

MacGregor, Stuart,

Gharahkhani, Puya,

Gockel, Ines,

Whiteman, David C.,

Ong, Jue-Sheng,

Lai, John,

Palles, Claire

2019

Overview

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. Gastroesophageal reflux disease (GERD) is a major risk factor for Barret’s esophagus (BE) and esophageal adenocarcinoma (EA). Here, An et al . report 25 genetic loci for GERD, many of which associate with BE and EA or with other traits such as BMI.

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Publisher

Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio

Subject

/ 45/43

/ 692/699/1503/1476/196

/ Adenocarcinoma