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.

Details

Title
Gastroesophageal reflux GWAS identifies risk loci that also associate with subsequent severe esophageal diseases
Author
An, Jiyuan 1 ; Puya Gharahkhani 1   VIAFID ORCID Logo  ; Law, Matthew H 1   VIAFID ORCID Logo  ; Jue-Sheng Ong 1   VIAFID ORCID Logo  ; Han, Xikun 1   VIAFID ORCID Logo  ; Olsen, Catherine M 2   VIAFID ORCID Logo  ; Neale, Rachel E 3 ; Lai, John 4 ; Vaughan, Tom L 5 ; Gockel, Ines 6 ; Thieme, René 6 ; Böhmer, Anne C 7   VIAFID ORCID Logo  ; Jankowski, Janusz 8 ; Fitzgerald, Rebecca C 9   VIAFID ORCID Logo  ; Schumacher, Johannes 10 ; Palles, Claire 11 ; Gammon, Marilie D 12 ; Corley, Douglas A 12 ; Shaheen, Nicholas J 12 ; Bird, Nigel C 12 ; Hardie, Laura J 12 ; Murray, Liam J 12 ; Reid, Brian J 12 ; Wong-Ho, Chow 12 ; Risch, Harvey A 12 ; Ye, Weimin 12 ; Liu, Geoffrey 12 ; Romero, Yvonne 12 ; Bernstein, Leslie 12 ; Wu, Anna H 12 ; Agee, M 13 ; Alipanahi, B 13 ; Auton, A 13 ; Bell, R K 13 ; Bryc, K 13 ; Elson, S L 13 ; Fontanillas, P 13 ; Furlotte, N A 13 ; Hinds, D A 13 ; Huber, K E 13 ; Kleinman, A 13 ; Litterman, N K 13 ; McIntyre, M H 13 ; Mountain, J L 13 ; Noblin, E S 13 ; Northover, C A M 13 ; Pitts, S J 13 ; Sathirapongsasuti, J Fah 13 ; Sazonova, O V 13 ; Shelton, J F 13 ; Shringarpure, S 13 ; Tian, C 13 ; Tung, J Y 13 ; Vacic, V 13 ; Wilson, C H 13 ; Whiteman, David C 2 ; MacGregor, Stuart 1   VIAFID ORCID Logo 

 Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia 
 Cancer Control, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia 
 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 
 Centre for Epidemiology and Biostatistics, The University of Melbourne, Melbourne, VIC, Australia 
 Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA 
 Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of Leipzig, Leipzig, Germany 
 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 
 Royal College of Surgeons in Ireland, Dublin, Ireland 
 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 
Pages
1-10
Publication year
2019
Publication date
Sep 2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2291324459
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.