Gastroesophageal reflux GWAS identifies risk loci that also associate with subsequent severe esophageal diseases.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
16 09 2019
16 09 2019
Historique:
received:
27
03
2019
accepted:
25
07
2019
entrez:
19
9
2019
pubmed:
19
9
2019
medline:
7
1
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31527586
doi: 10.1038/s41467-019-11968-2
pii: 10.1038/s41467-019-11968-2
pmc: PMC6746768
doi:
Types de publication
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4219Subventions
Organisme : NCI NIH HHS
ID : U54 CA163060
Pays : United States
Investigateurs
Marilie D Gammon
(MD)
Douglas A Corley
(DA)
Nicholas J Shaheen
(NJ)
Nigel C Bird
(NC)
Laura J Hardie
(LJ)
Liam J Murray
(LJ)
Brian J Reid
(BJ)
Wong-Ho Chow
(WH)
Harvey A Risch
(HA)
Weimin Ye
(W)
Geoffrey Liu
(G)
Yvonne Romero
(Y)
Leslie Bernstein
(L)
Anna H Wu
(AH)
M Agee
(M)
B Alipanahi
(B)
A Auton
(A)
R K Bell
(RK)
K Bryc
(K)
S L Elson
(SL)
P Fontanillas
(P)
N A Furlotte
(NA)
D A Hinds
(DA)
K E Huber
(KE)
A Kleinman
(A)
N K Litterman
(NK)
M H McIntyre
(MH)
J L Mountain
(JL)
E S Noblin
(ES)
C A M Northover
(CAM)
S J Pitts
(SJ)
J Fah Sathirapongsasuti
(JF)
O V Sazonova
(OV)
J F Shelton
(JF)
S Shringarpure
(S)
C Tian
(C)
J Y Tung
(JY)
V Vacic
(V)
C H Wilson
(CH)
Commentaires et corrections
Type : ErratumIn
Références
Nat Genet. 2018 May;50(5):668-681
pubmed: 29700475
Gut. 1970 Aug;11(8):715-9
pubmed: 4919260
Am J Hum Genet. 2011 Jan 7;88(1):76-82
pubmed: 21167468
Hum Mol Genet. 2016 Feb 15;25(4):828-35
pubmed: 26704365
Sci Rep. 2017 Oct 18;7(1):13429
pubmed: 29044141
Dig Dis Sci. 2017 Apr;62(4):994-1001
pubmed: 28116594
Cancer Res. 2001 Nov 15;61(22):8284-9
pubmed: 11719461
Nat Genet. 2018 Aug;50(8):1067-1071
pubmed: 30054594
PLoS Comput Biol. 2015 Apr 17;11(4):e1004219
pubmed: 25885710
Am J Gastroenterol. 2001 Jul;96(7):2033-40
pubmed: 11467629
Nat Genet. 2015 Mar;47(3):284-90
pubmed: 25642633
World J Gastrointest Pharmacol Ther. 2014 Aug 6;5(3):105-12
pubmed: 25133039
Gut. 2014 Jun;63(6):871-80
pubmed: 23853213
Hum Mol Genet. 2018 Oct 15;27(20):3641-3649
pubmed: 30124842
J Natl Cancer Inst. 2013 Nov 20;105(22):1711-8
pubmed: 24168968
Genetics. 2018 Apr;208(4):1397-1408
pubmed: 29429966
Nat Genet. 2016 Oct;48(10):1284-1287
pubmed: 27571263
Nat Genet. 2015 Mar;47(3):291-5
pubmed: 25642630
Neurogastroenterol Motil. 2017 Feb;29(2):
pubmed: 27485664
Gigascience. 2015 Feb 25;4:7
pubmed: 25722852
Gastroenterology. 2002 Jan;122(1):55-9
pubmed: 11781280
Nat Genet. 2012 Mar 18;44(4):369-75, S1-3
pubmed: 22426310
Cancer Res. 2010 Sep 1;70(17):6787-96
pubmed: 20647328
PLoS One. 2014 Jul 30;9(7):e103508
pubmed: 25075959
Gastroenterology. 2015 Feb;148(2):367-78
pubmed: 25447851
Int J Epidemiol. 2012 Aug;41(4):929-929i
pubmed: 22933644
Nat Genet. 2013 Dec;45(12):1487-93
pubmed: 24121790
Gut. 2003 Aug;52(8):1085-9
pubmed: 12865263
Pharmacoeconomics. 2014 Aug;32(8):745-58
pubmed: 24807469
Nat Genet. 2012 Oct;44(10):1131-6
pubmed: 22961001
Nat Commun. 2015 Jan 19;6:5890
pubmed: 25597830
FASEB J. 2019 Feb;33(2):1972-1988
pubmed: 30226808
Nat Genet. 2018 Jul;50(7):956-967
pubmed: 29955180
J Carcinog. 2015 May 21;14:5
pubmed: 26085818
Bioinformatics. 2010 Sep 1;26(17):2190-1
pubmed: 20616382
Nat Genet. 2016 Jul;48(7):811-6
pubmed: 27270109
Br J Cancer. 2015 Apr 14;112(8):1384-91
pubmed: 25867265
Nat Genet. 2018 Aug;50(8):1112-1121
pubmed: 30038396
Bioinformatics. 2017 Jan 15;33(2):272-279
pubmed: 27663502
Nature. 2016 May 11;533(7604):539-42
pubmed: 27225129
J Gastroenterol Hepatol. 2016 Jun;31(6):1141-6
pubmed: 26749521
Gut. 2005 May;54(5):710-7
pubmed: 15831922
Am J Hum Genet. 2007 Sep;81(3):559-75
pubmed: 17701901
Gastroenterology. 2018 Jan;154(2):390-405
pubmed: 28780073
Nat Genet. 2015 Sep;47(9):1091-8
pubmed: 26258848
Lancet Oncol. 2016 Oct;17(10):1363-1373
pubmed: 27527254