Multi-ancestry genome-wide association study of asthma exacerbations.

Asthma / genetics Genetic Predisposition to Disease Genome-Wide Association Study Hispanic or Latino / genetics Humans Polymorphism, Single Nucleotide Quality of Life
EXTL2 PANK1 GWAS asthma exacerbations single-nucleotide polymorphism

Journal

Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology
ISSN: 1399-3038
Titre abrégé: Pediatr Allergy Immunol
Pays: England
ID NLM: 9106718

Informations de publication

Date de publication:
06 2022
Historique:
revised: 01 05 2022
received: 17 03 2022
accepted: 04 05 2022
entrez: 27 6 2022
pubmed: 28 6 2022
medline: 29 6 2022
Statut: ppublish

Résumé

Asthma exacerbations are a serious public health concern due to high healthcare resource utilization, work/school productivity loss, impact on quality of life, and risk of mortality. The genetic basis of asthma exacerbations has been studied in several populations, but no prior study has performed a multi-ancestry meta-analysis of genome-wide association studies (meta-GWAS) for this trait. We aimed to identify common genetic loci associated with asthma exacerbations across diverse populations and to assess their functional role in regulating DNA methylation and gene expression. A meta-GWAS of asthma exacerbations in 4989 Europeans, 2181 Hispanics/Latinos, 1250 Singaporean Chinese, and 972 African Americans analyzed 9.6 million genetic variants. Suggestively associated variants (p ≤ 5 × 10 One hundred and twenty-six independent variants were suggestively associated with asthma exacerbations in the discovery phase. Two variants independently replicated: rs12091010 located at vascular cell adhesion molecule-1/exostosin like glycosyltransferase-2 (VCAM1/EXTL2) (discovery: odds ratio (OR This multi-ancestry study revealed novel suggestive regulatory loci for asthma exacerbations located in genomic regions participating in inflammation and host defense.

Sections du résumé

BACKGROUND
Asthma exacerbations are a serious public health concern due to high healthcare resource utilization, work/school productivity loss, impact on quality of life, and risk of mortality. The genetic basis of asthma exacerbations has been studied in several populations, but no prior study has performed a multi-ancestry meta-analysis of genome-wide association studies (meta-GWAS) for this trait. We aimed to identify common genetic loci associated with asthma exacerbations across diverse populations and to assess their functional role in regulating DNA methylation and gene expression.
METHODS
A meta-GWAS of asthma exacerbations in 4989 Europeans, 2181 Hispanics/Latinos, 1250 Singaporean Chinese, and 972 African Americans analyzed 9.6 million genetic variants. Suggestively associated variants (p ≤ 5 × 10
RESULTS
One hundred and twenty-six independent variants were suggestively associated with asthma exacerbations in the discovery phase. Two variants independently replicated: rs12091010 located at vascular cell adhesion molecule-1/exostosin like glycosyltransferase-2 (VCAM1/EXTL2) (discovery: odds ratio (OR
CONCLUSIONS
This multi-ancestry study revealed novel suggestive regulatory loci for asthma exacerbations located in genomic regions participating in inflammation and host defense.

Identifiants

DOI: 10.1111/pai.13802 PMID: 35754128 PMC: PMC9671132
pubmed: 35754128
doi: 10.1111/pai.13802
pmc: PMC9671132
mid: NIHMS1847104
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

e13802

Subventions

Organisme : NIEHS NIH HHS
ID : R01 ES015794
Pays : United States
Organisme : Wellcome Trust
ID : 099177/Z/12/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_19009
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL141992
Pays : United States
Organisme : Medical Research Council
ID : MR/L006758/1
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL141845
Pays : United States
Organisme : Medical Research Council
ID : MC_PC_15018
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL135156
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG009080
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL128439
Pays : United States
Organisme : NIEHS NIH HHS
ID : R21 ES024844
Pays : United States
Organisme : NIMHD NIH HHS
ID : R56 MD013312
Pays : United States
Organisme : Wellcome Trust
ID : 102215/2/13/2
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL142992
Pays : United States
Organisme : NHLBI NIH HHS
ID : K01 HL138098
Pays : United States
Organisme : NIMHD NIH HHS
ID : P60 MD006902
Pays : United States
Organisme : Medical Research Council
ID : G9815508
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL117004
Pays : United States
Organisme : NIGMS NIH HHS
ID : RL5 GM118984
Pays : United States
Organisme : NIMHD NIH HHS
ID : R01 MD010443
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 2022 The Authors. Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.

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Auteurs

Esther Herrera-Luis (E)

Genomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology and Genetics, Universidad de La Laguna (ULL), San Cristóbal de La Laguna, Tenerife, Spain.
ORCID: 0000-0003-4150-5454

Victor E Ortega (VE)

Division of Respiratory Medicine, Department of Internal Medicine, Mayo Clinic, Scottsdale, Arizona, USA.

Elizabeth J Ampleford (EJ)

Department of Internal Medicine, Center for Precision Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.

Yang Yie Sio (YY)

Department of Biological Sciences, National University of Singapore, Singapore City, Singapore.

Raquel Granell (R)

MRC Integrative Epidemiology Unit (IEU), Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
ORCID: 0000-0002-4890-4012

Emmely de Roos (E)

Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.

Natalie Terzikhan (N)

Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.

Ernesto Elorduy Vergara (EE)

Institute of Computation Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich, Germany.

Natalia Hernandez-Pacheco (N)

Department of Clinical Sciences and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
ORCID: 0000-0002-6313-1847

Javier Perez-Garcia (J)

Genomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology and Genetics, Universidad de La Laguna (ULL), San Cristóbal de La Laguna, Tenerife, Spain.
ORCID: 0000-0001-7813-4381

Elena Martin-Gonzalez (E)

Genomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology and Genetics, Universidad de La Laguna (ULL), San Cristóbal de La Laguna, Tenerife, Spain.

Fabian Lorenzo-Diaz (F)

Genomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology and Genetics, Universidad de La Laguna (ULL), San Cristóbal de La Laguna, Tenerife, Spain.
Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC), Universidad de La Laguna (ULL), San Cristóbal de La Laguna, Tenerife, Spain.
ORCID: 0000-0002-3398-198X

Simone Hashimoto (S)

Department of Respiratory Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
ORCID: 0000-0001-8995-3817

Paul Brinkman (P)

Department of Respiratory Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

Andrea L Jorgensen (AL)

Department of Health Data Science, Institute of Population Health, University of Liverpool, Liverpool, UK.

Qi Yan (Q)

Department of Obstetrics and Gynecology, Columbia University Irving Medical Center, New York, New York, USA.
ORCID: 0000-0002-5236-9673

Erick Forno (E)

Division of Pediatric Pulmonary Medicine, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
ORCID: 0000-0001-6497-9885

Susanne J Vijverberg (SJ)

Department of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Division of Pharmacoepidemiology and Clinical Pharmacology, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
Department of Paediatric Respiratory Medicine and Allergy, Emma's Children Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
ORCID: 0000-0002-4579-4081

Ryan Lethem (R)

MRC Integrative Epidemiology Unit (IEU), Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.

Antonio Espuela-Ortiz (A)

Genomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology and Genetics, Universidad de La Laguna (ULL), San Cristóbal de La Laguna, Tenerife, Spain.
ORCID: 0000-0003-0572-9549

Mario Gorenjak (M)

Center for Human Molecular Genetics and Pharmacogenomics, Faculty of Medicine, University of Maribor, Maribor, Slovenia.
ORCID: 0000-0003-4208-9683

Celeste Eng (C)

Department of Medicine, University of California San Francisco, San Francisco, California, USA.

Ruperto González-Pérez (R)

Allergy Department, Hospital Universitario de Canarias, Santa Cruz de Tenerife, Tenerife, Spain.
Severe Asthma Unit, Allergy Department, Hospital Universitario de Canarias, Santa Cruz de Tenerife, Tenerife, Spain.

José M Hernández-Pérez (JM)

Pulmonary Medicine, Hospital Universitario de N.S de Candelaria, Santa Cruz de Tenerife, Spain.
Pulmonary Medicine, Hospital General de La Palma, La Palma, Santa Cruz de Tenerife, Spain.
ORCID: 0000-0002-2920-212X

Paloma Poza-Guedes (P)

Allergy Department, Hospital Universitario de Canarias, Santa Cruz de Tenerife, Tenerife, Spain.
Severe Asthma Unit, Allergy Department, Hospital Universitario de Canarias, Santa Cruz de Tenerife, Tenerife, Spain.
ORCID: 0000-0001-8516-6648

Olaia Sardón (O)

Division of Pediatric Respiratory Medicine, Hospital Universitario Donostia, San Sebastián, Spain.
Department of Pediatrics, University of the Basque Country (UPV/EHU), San Sebastián, Spain.

Paula Corcuera (P)

Division of Pediatric Respiratory Medicine, Hospital Universitario Donostia, San Sebastián, Spain.
ORCID: 0000-0001-8661-7033

Greg A Hawkins (GA)

Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.

Annalisa Marsico (A)

Computational Health Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich, Germany.

Thomas Bahmer (T)

LungenClinic Grosshansdorf, Pneumology, Grosshansdorf, Germany.
Airway Research Center North (ARCN), Members of the Germany Center for Lung Research (DZL), Grosshansdorf, Germany.

Klaus F Rabe (KF)

LungenClinic Grosshansdorf, Pneumology, Grosshansdorf, Germany.
Airway Research Center North (ARCN), Members of the Germany Center for Lung Research (DZL), Grosshansdorf, Germany.

Gesine Hansen (G)

Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.

Matthias Volkmar Kopp (MV)

Division of Pediatric Pneumology & Allergology, University Medical Center Schleswig-Holstein, Lübeck, Germany.
Airway Research Center North (ARCN), Members of the Germany Center for Lung Research (DZL), Lübeck, Germany.
Department of Paediatric Respiratory Medicine, Inselspital, University Children's Hospital of Bern, University of Bern, Bern, Switzerland.

Raimon Rios (R)

Programa de Pós Graduação em Imunologia (PPGIm), Instituto de Ciências da Saúde, Universidade Federal da Bahia (UFBA), Salvador, Brazil.

Maria Jesus Cruz (MJ)

CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
Servicio de Neumología, Hospital Vall d'Hebron, Barcelona, Spain.

Francisco-Javier González-Barcala (FJ)

Servicio de Neumología, Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, Spain.

José María Olaguibel (JM)

CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
Servicio de Alergología, Complejo Hospitalario de Navarra, Pamplona, Navarra, Spain.
ORCID: 0000-0002-9126-4559

Vicente Plaza (V)

CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
Departamento de Medicina Respiratoria, Hospital de la Santa Creu i Sant Pau, Instituto de Investigación Biomédica Sant Pau (IIB Sant Pau), Barcelona, Spain.
ORCID: 0000-0003-2567-5496

Santiago Quirce (S)

CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
Department of Allergy, La Paz University Hospital, IdiPAZ, Madrid, Spain.
ORCID: 0000-0001-8086-0921

Glorisa Canino (G)

Behavioral Sciences Research Institute, University of Puerto Rico, San Juan, Puerto Rico.

Michelle Cloutier (M)

Department of Pediatrics, University of Connecticut, Farmington, Connecticut, USA.
ORCID: 0000-0001-8316-6409

Victoria Del Pozo (V)

CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
Immunology Department, Instituto de Investigación Sanitaria Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain.
ORCID: 0000-0001-6228-1969

Jose R Rodriguez-Santana (JR)

Centro de Neumología Pediátrica, San Juan, Puerto Rico.

Javier Korta-Murua (J)

Department of Pediatrics, University of the Basque Country (UPV/EHU), San Sebastián, Spain.

Jesús Villar (J)

CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
Multidisciplinary Organ Dysfunction Evaluation Research Network, Research Unit, Hospital Universitario Dr. Negrín, Las Palmas de Gran Canaria, Spain.

Uroš Potočnik (U)

Laboratory for Biochemistry, Molecular Biology and Genomics, Faculty for Chemistry and Chemical Engineering, University of Maribor, Maribor, Slovenia.

Camila Figueiredo (C)

Instituto de Ciências da Saúde, Universidade Federal da Bahia, Salvador, Brazil.
ORCID: 0000-0003-1356-6188

Michael Kabesch (M)

Department of Paediatric Pneumology and Allergy, University Children's Hospital Regensburg (KUNO), Regensburg, Germany.

Somnath Mukhopadhyay (S)

Academic Department of Paediatrics, Brighton and Sussex Medical School, Royal Alexandra Children's Hospital, Brighton, UK.
Population Pharmacogenetics Group, Biomedical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.

Munir Pirmohamed (M)

Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.
ORCID: 0000-0002-7534-7266

Daniel B Hawcutt (DB)

Department of Women's and Children's Health, University of Liverpool, Liverpool, UK.
Alder Hey Children's Hospital, Liverpool, UK.
NIHR Alder Hey Clinical Research Facility, Alder Hey Children's Hospital, Liverpool, UK.
ORCID: 0000-0002-8120-6507

Erik Melén (E)

Department of Clinical Sciences and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
Sachs' Children's Hospital, South General Hospital, Stockholm, Sweden.
ORCID: 0000-0002-8248-0663

Colin N Palmer (CN)

Population Pharmacogenetics Group, Biomedical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
ORCID: 0000-0002-6415-6560

Steve Turner (S)

Child Health, University of Aberdeen, Aberdeen, UK.
ORCID: 0000-0001-8393-5060

Anke H Maitland-van der Zee (AH)

Department of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Division of Pharmacoepidemiology and Clinical Pharmacology, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
Department of Paediatric Respiratory Medicine and Allergy, Emma's Children Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
ORCID: 0000-0002-0414-3442

Erika von Mutius (E)

Institute for Asthma and Allergy Prevention, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich, Germany.
Dr von Hauner Children's Hospital, Ludwig-Maximilians-Universität, Munich, Germany.
Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research, Munich, Germany.
ORCID: 0000-0002-8893-4515

Juan C Celedón (JC)

Division of Pediatric Pulmonary Medicine, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
ORCID: 0000-0002-6139-5320

Guy Brusselle (G)

Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
Department of Respiratory Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
ORCID: 0000-0001-7021-8505

Fook Tim Chew (FT)

Department of Biological Sciences, National University of Singapore, Singapore City, Singapore.
ORCID: 0000-0003-1337-5146

Eugene Bleecker (E)

Division of Genetics, Genomics, and Precision Medicine, Department of Internal Medicine, University of Arizona College of Medicine, Tucson, Arizona, USA.

Deborah Meyers (D)

Division of Genetics, Genomics, and Precision Medicine, Department of Internal Medicine, University of Arizona College of Medicine, Tucson, Arizona, USA.

Esteban G Burchard (EG)

Severe Asthma Unit, Allergy Department, Hospital Universitario de Canarias, Santa Cruz de Tenerife, Tenerife, Spain.
Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, USA.
ORCID: 0000-0001-7475-2035

Maria Pino-Yanes (M)

Genomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology and Genetics, Universidad de La Laguna (ULL), San Cristóbal de La Laguna, Tenerife, Spain.
CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
Instituto de Tecnologías Biomédicas (ITB), Universidad de La Laguna (ULL), San Cristóbal de La Laguna, Tenerife, Spain.
ORCID: 0000-0003-0332-437X

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Classifications MeSH

questionsmedicales.fr › Maladies du système immunitaire › Hypersensibilité › Hypersensibilité immédiate › Hypersensibilité respiratoire › Asthme › Multi-ancestry genome-wide association study...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Prédisposition génétique à une maladie › Multi-ancestry genome-wide association study...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › Multi-ancestry genome-wide association study...
questionsmedicales.fr › Personnes › Nord-Américains › Groupes de population aux États-Unis › Hispanique ou Latino › Multi-ancestry genome-wide association study...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Multi-ancestry genome-wide association study...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Polymorphisme de nucléotide simple › Multi-ancestry genome-wide association study...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Mesures épidémiologiques › Démographie › État de santé › Qualité de vie › Multi-ancestry genome-wide association study...