A pilot genome-wide association study meta-analysis of gastroparesis.

Humans Genome-Wide Association Study Gastroparesis / genetics Genetic Predisposition to Disease Abdominal Pain
PXDNL abdominal pain delayed gastric emptying diabetes enteric nervous system gastroparesis genetics immune dysregulation inflammation motor function

Journal

United European gastroenterology journal
ISSN: 2050-6414
Titre abrégé: United European Gastroenterol J
Pays: England
ID NLM: 101606807

Informations de publication

Date de publication:
10 2023
Historique:
received: 24 03 2023
accepted: 15 06 2023
medline: 23 10 2023
pubmed: 9 9 2023
entrez: 9 9 2023
Statut: ppublish

Résumé

Gastroparesis (GP) is characterized by delayed gastric emptying in the absence of mechanical obstruction. Genetic predisposition may play a role; however, investigation at the genome-wide level has not been performed. We carried out a genome-wide association study (GWAS) meta-analysis on (i) 478 GP patients from the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium (GpCRC) compared to 9931 population-based controls from the University of Michigan Health and Retirement Study; and (ii) 402 GP cases compared to 48,340 non-gastroparesis controls from the Michigan Genomics Initiative. Associations for 5,811,784 high-quality SNPs were tested on a total of 880 GP patients and 58,271 controls, using logistic mixed models adjusted for age, sex, and principal components. Gene mapping was obtained based on genomic position and expression quantitative trait loci, and a gene-set network enrichment analysis was performed. Genetic associations with clinical data were tested in GpCRC patients. Protein expression of selected candidate genes was determined in full thickness gastric biopsies from GpCRC patients and controls. While no SNP associations were detected at strict significance (p ≤ 5 × 10 We report preliminary GWAS findings for GP, which highlight candidate genes and pathways related to immune and sensory-motor dysregulation. Larger studies are needed to validate and expand these findings in independent datasets.

Sections du résumé

BACKGROUND
Gastroparesis (GP) is characterized by delayed gastric emptying in the absence of mechanical obstruction.
OBJECTIVE
Genetic predisposition may play a role; however, investigation at the genome-wide level has not been performed.
METHODS
We carried out a genome-wide association study (GWAS) meta-analysis on (i) 478 GP patients from the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium (GpCRC) compared to 9931 population-based controls from the University of Michigan Health and Retirement Study; and (ii) 402 GP cases compared to 48,340 non-gastroparesis controls from the Michigan Genomics Initiative. Associations for 5,811,784 high-quality SNPs were tested on a total of 880 GP patients and 58,271 controls, using logistic mixed models adjusted for age, sex, and principal components. Gene mapping was obtained based on genomic position and expression quantitative trait loci, and a gene-set network enrichment analysis was performed. Genetic associations with clinical data were tested in GpCRC patients. Protein expression of selected candidate genes was determined in full thickness gastric biopsies from GpCRC patients and controls.
RESULTS
While no SNP associations were detected at strict significance (p ≤ 5 × 10
CONCLUSION
We report preliminary GWAS findings for GP, which highlight candidate genes and pathways related to immune and sensory-motor dysregulation. Larger studies are needed to validate and expand these findings in independent datasets.

Identifiants

DOI: 10.1002/ueg2.12453 PMID: 37688361 PMC: PMC10576603
pubmed: 37688361
doi: 10.1002/ueg2.12453
pmc: PMC10576603
doi:

Types de publication

Meta-Analysis Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

784-796

Subventions

Organisme : NIDDK NIH HHS
ID : U24 DK074008
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK112194
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK074007
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK073975
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK074035
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000424
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK073985
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK073983
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000135
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK112193
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK073974
Pays : United States

Informations de copyright

© 2023 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.

Références

Clin Transl Gastroenterol. 2022 Apr 01;13(4):e00474
pubmed: 35297797
PLoS Genet. 2019 Nov 18;15(11):e1008104
pubmed: 31738745
Front Immunol. 2019 Jul 03;10:1462
pubmed: 31333642
Brain Res Bull. 2007 May 30;72(4-6):194-200
pubmed: 17452281
Gastroenterology. 2011 May;140(5):1575-85.e8
pubmed: 21300066
Work Aging Retire. 2018 Jan;4(1):1-9
pubmed: 29423243
Bioinformatics. 2010 Sep 1;26(17):2190-1
pubmed: 20616382
Hum Immunol. 1999 Jul;60(7):591-7
pubmed: 10426276
BMC Med Genomics. 2018 Aug 07;11(1):62
pubmed: 30086735
Clin Gastroenterol Hepatol. 2022 Dec;20(12):2684-2695.e3
pubmed: 35688353
Gastroenterology. 2010 Jun;138(7):2399-409, 2409.e1
pubmed: 20178793
Nat Commun. 2014 Oct 16;5:4992
pubmed: 25318560
Nat Rev Gastroenterol Hepatol. 2022 Nov;19(11):689-702
pubmed: 35948782
Nat Protoc. 2007;2(10):2492-501
pubmed: 17947991
Genomics. 1997 Jun 1;42(2):311-8
pubmed: 9192852
Gut. 2019 Dec;68(12):2238-2250
pubmed: 31563877
Neurogastroenterol Motil. 2021 Aug;33(8):e14237
pubmed: 34399024
J Gastroenterol Hepatol. 2022 Mar;37(3):440-445
pubmed: 34750862
Nat Genet. 2018 Sep;50(9):1335-1341
pubmed: 30104761
World J Gastroenterol. 2018 Nov 28;24(44):4979-4988
pubmed: 30510373
Am J Physiol Gastrointest Liver Physiol. 2019 Nov 1;317(5):G716-G726
pubmed: 31482734
Curr Diab Rep. 2011 Dec;11(6):533-42
pubmed: 21912932
PLoS One. 2017 Nov 21;12(11):e0187772
pubmed: 29161307
Qual Life Res. 2004 May;13(4):833-44
pubmed: 15129893
Neurogastroenterol Motil. 2017 Jun;29(6):
pubmed: 28066953
J Neurogastroenterol Motil. 2012 Jan;18(1):34-42
pubmed: 22323986
United European Gastroenterol J. 2023 Oct;11(8):784-796
pubmed: 37688361
Front Genet. 2021 Jun 17;12:683946
pubmed: 34220961
Gastroenterology. 2022 Jan;162(1):109-121.e5
pubmed: 34624355
Cell Mol Gastroenterol Hepatol. 2022;13(5):1483-1509
pubmed: 35093588
Int J Environ Res Public Health. 2021 Jan 29;18(3):
pubmed: 33572734
J Biomed Sci. 2021 May 13;28(1):37
pubmed: 33985508
Neurosignals. 2014;22(1):1-13
pubmed: 24356576
Qual Life Res. 2004 Dec;13(10):1737-49
pubmed: 15651544
Gastroenterology. 2011 Jul;141(1):259-68, 268.e1-8
pubmed: 21440550
Cell Genom. 2023 Jan 31;3(2):100257
pubmed: 36819667
Front Immunol. 2018 Jul 30;9:1744
pubmed: 30105024
Stroke. 2013 Oct;44(10):2694-702
pubmed: 24021684
Am J Gastroenterol. 2022 Aug 1;117(8):1197-1220
pubmed: 35926490

Auteurs

Leticia Camargo Tavares (LC)

School of Biological Sciences, Monash University, Melbourne, Victoria, Australia.

Tenghao Zheng (T)

School of Biological Sciences, Monash University, Melbourne, Victoria, Australia.

Madeline Kwicklis (M)

Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.

Emily Mitchell (E)

Johns Hopkins University Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.

Anita Pandit (A)

Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.

Suraj Pullapantula (S)

Mayo Clinic, Rochester, Minnesota, USA.

Cheryl Bernard (C)

Mayo Clinic, Rochester, Minnesota, USA.

Maris Teder-Laving (M)

Institute of Genomics, University of Tartu, Tartu, Estonia.

Francine Z Marques (FZ)

School of Biological Sciences, Monash University, Melbourne, Victoria, Australia.
Heart Failure Research Group, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.

Tonu Esko (T)

Institute of Genomics, University of Tartu, Tartu, Estonia.

Braden Kuo (B)

Massachusetts General Hospital, Boston, Massachusetts, USA.

Robert J Shulman (RJ)

Baylor College of Medicine, Houston, Texas, USA.

Bruno P Chumpitazi (BP)

Baylor College of Medicine, Houston, Texas, USA.

Kenneth L Koch (KL)

Wake Forest University, Winston-Salem, North Carolina, USA.

Irene Sarosiek (I)

Texas Tech University Health Sciences Center, El Paso, Texas, USA.

Thomas L Abell (TL)

University of Louisville, Louisville, Kentucky, USA.

Richard W McCallum (RW)

Texas Tech University Health Sciences Center, El Paso, Texas, USA.

Henry P Parkman (HP)

Temple University, Philadelphia, Pennsylvania, USA.

Pankaj J Pasricha (PJ)

Mayo Clinic, Phoenix, Arizona, USA.

Frank A Hamilton (FA)

National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, USA.

James Tonascia (J)

Johns Hopkins University Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.

Matthew Zawistowski (M)

Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.

Gianrico Farrugia (G)

Mayo Clinic, Rochester, Minnesota, USA.
ORCID: 0000-0003-3473-5235

Madhusudan Grover (M)

Mayo Clinic, Rochester, Minnesota, USA.
ORCID: 0000-0001-5092-0831

Mauro D'Amato (M)

School of Biological Sciences, Monash University, Melbourne, Victoria, Australia.
Gastrointestinal Genetics Lab, CIC BioGUNE-BRTA, Derio, Spain.
Ikerbasque, Basque Foundation for Science, Bilbao, Spain.
Department of Medicine and Surgery, LUM University, Casamassima, Italy.

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