A genome-wide association meta-analysis identifies new eosinophilic esophagitis loci.

Eosinophilic Esophagitis / genetics Female Genetic Loci Genetic Predisposition to Disease Genome-Wide Association Study Humans Male Polymorphism, Single Nucleotide
Eosinophilic esophagitis GWAS genetic correlation genetic variants

Journal

The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002

Informations de publication

Date de publication:
03 2022
Historique:
received: 20 10 2020
revised: 24 08 2021
accepted: 31 08 2021
pubmed: 11 9 2021
medline: 26 4 2022
entrez: 10 9 2021
Statut: ppublish

Résumé

Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder of the esophagus marked by eosinophilic infiltration. Cumulative evidence indicates that the risk of EoE involves the complex interplay of both genetic and environmental factors. Because only a few genetic loci have been identified in EoE, the genetic underpinning of EoE remains largely elusive. We sought to identify genetic loci associated with EoE. Four EoE cohorts were genotyped using the Illumina single nucleotide polymorphism array platform, totaling 1,930 cases and 13,634 controls of European ancestry. Genotype imputation was performed with the Michigan Imputation Server using the Trans-Omics for Precision Medicine reference panel including whole-genome sequencing data from more than 100,000 individuals. Meta-analysis was conducted to identify potential novel genetic loci associated with EoE. Our study identified 11 new genome-wide significant loci, of which 6 are common variant loci, including 5q31.1 (rs2106984, P = 4.16 × 10 Our findings demonstrate shared genetic underpinnings between EoE and other immune-mediated diseases and provide novel candidate genes for therapeutic target identification and prioritization.

Sections du résumé

BACKGROUND
Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder of the esophagus marked by eosinophilic infiltration. Cumulative evidence indicates that the risk of EoE involves the complex interplay of both genetic and environmental factors. Because only a few genetic loci have been identified in EoE, the genetic underpinning of EoE remains largely elusive.
OBJECTIVE
We sought to identify genetic loci associated with EoE.
METHODS
Four EoE cohorts were genotyped using the Illumina single nucleotide polymorphism array platform, totaling 1,930 cases and 13,634 controls of European ancestry. Genotype imputation was performed with the Michigan Imputation Server using the Trans-Omics for Precision Medicine reference panel including whole-genome sequencing data from more than 100,000 individuals. Meta-analysis was conducted to identify potential novel genetic loci associated with EoE.
RESULTS
Our study identified 11 new genome-wide significant loci, of which 6 are common variant loci, including 5q31.1 (rs2106984, P = 4.16 × 10
CONCLUSIONS
Our findings demonstrate shared genetic underpinnings between EoE and other immune-mediated diseases and provide novel candidate genes for therapeutic target identification and prioritization.

Identifiants

DOI: 10.1016/j.jaci.2021.08.018 PMID: 34506852 PMC: PMC9579995
pubmed: 34506852
pii: S0091-6749(21)01358-0
doi: 10.1016/j.jaci.2021.08.018
pmc: PMC9579995
mid: NIHMS1743544
pii:
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

988-998

Subventions

Organisme : NHGRI NIH HHS
ID : U01 HG006830
Pays : United States

Informations de copyright

Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

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Auteurs

Xiao Chang (X)

Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pa.

Michael March (M)

Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pa.

Frank Mentch (F)

Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pa.

Kenny Nguyen (K)

Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pa.

Joseph Glessner (J)

Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pa.

Huiqi Qu (H)

Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pa.

Yichuan Liu (Y)

Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pa.

Glen Furuta (G)

Digestive Health Institute, Section of Pediatric Gastroenterology, Hepatology and Nutrition, Children's Hospital Colorado, Aurora, Colo; Gastrointestinal Eosinophilic Diseases Program, Department of Pediatrics, Mucosal Inflammation Program, University of Colorado School of Medicine, Aurora, Colo.

Seema Aceves (S)

Division of Allergy, Immunology, Department of Pediatrics and Medicine, University of California, San Diego, Calif; Rady Children's Hospital, San Diego, Calif.

Nirmala Gonsalves (N)

Division of Gastroenterology & Hepatology, Northwestern University, The Feinberg School of Medicine, Chicago, Ill.

Kari Nadeau (K)

Stanford University School of Medicine, Lucile Packard Children's Hospital, Stanford Hospital and Clinics, Division of Allergy, Immunology, and Rheumatology, Palo Alto, Calif.

Antonella Cianferoni (A)

Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pa; Division of Allergy and Immunology, The Children's Hospital of Philadelphia, Philadelphia, Pa.

Jonathan Spergel (J)

Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pa; Division of Allergy and Immunology, The Children's Hospital of Philadelphia, Philadelphia, Pa.

Patrick Sleiman (P)

Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pa; Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pa; Divisions of Human Genetics and Pulmonary Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pa.

Hakon Hakonarson (H)

Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pa; Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pa; Divisions of Human Genetics and Pulmonary Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pa; Faculty of Medicine, University of Iceland, Reykjavik, Iceland. Electronic address: hakonarson@chop.edu.

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Classifications MeSH

questionsmedicales.fr › Maladies du système immunitaire › Hypersensibilité › Hypersensibilité immédiate › Oesophagite à éosinophiles › A genome-wide association meta-analysis...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Locus génétiques › A genome-wide association meta-analysis...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Prédisposition génétique à une maladie › A genome-wide association meta-analysis...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › A genome-wide association meta-analysis...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › A genome-wide association meta-analysis...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Polymorphisme de nucléotide simple › A genome-wide association meta-analysis...