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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.
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1 Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
2 Cancer Control, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
3 Cancer Aetiology and Prevention, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia; School of Public Health, The University of Queensland, Brisbane, QLD, Australia; School of Public Health and Social Work, the Queensland University of Technology, Brisbane, QLD, Australia
4 Centre for Epidemiology and Biostatistics, The University of Melbourne, Melbourne, VIC, Australia
5 Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
6 Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of Leipzig, Leipzig, Germany
7 Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany; Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany
8 Royal College of Surgeons in Ireland, Dublin, Ireland
9 Medical Research Council (MRC) Cancer Unit, Hutchison-MRC Research Centre and University of Cambridge, Cambridge, UK
10 Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany; Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany; Center for Human Genetics, University Hospital of Marburg, Marburg, Germany
11 Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK
12 International Barrett’s and Esophageal Adenocarcinoma Consortium, Mountain View, CA, USA
13 23andMe, Inc., Mountain View, CA, USA