An admixture mapping meta-analysis implicates genetic variation at 18q21 with asthma susceptibility in Latinos.

Asthma / genetics Chromosome Mapping Chromosomes, Human, Pair 18 Genetic Predisposition to Disease Hispanic or Latino / genetics Humans Polymorphism, Single Nucleotide Smad2 Protein / genetics
Asthma Latinos SMAD2 admixture mapping asthma exacerbations gene expression meta-analysis rare variation targeted sequencing

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 2019
Historique:
received: 13 10 2015
revised: 20 08 2016
accepted: 29 08 2016
pubmed: 12 9 2018
medline: 17 3 2020
entrez: 12 9 2018
Statut: ppublish

Résumé

Asthma is a common but complex disease with racial/ethnic differences in prevalence, morbidity, and response to therapies. We sought to perform an analysis of genetic ancestry to identify new loci that contribute to asthma susceptibility. We leveraged the mixed ancestry of 3902 Latinos and performed an admixture mapping meta-analysis for asthma susceptibility. We replicated associations in an independent study of 3774 Latinos, performed targeted sequencing for fine mapping, and tested for disease correlations with gene expression in the whole blood of more than 500 subjects from 3 racial/ethnic groups. We identified a genome-wide significant admixture mapping peak at 18q21 in Latinos (P = 6.8 × 10 Ancestry at 18q21 was significantly associated with asthma in Latinos and implicated multiple ancestry-informative noncoding variants upstream of SMAD2 with asthma susceptibility. Furthermore, decreased SMAD2 expression in blood was strongly associated with increased asthma risk and increased exacerbations.

Sections du résumé

BACKGROUND
Asthma is a common but complex disease with racial/ethnic differences in prevalence, morbidity, and response to therapies.
OBJECTIVE
We sought to perform an analysis of genetic ancestry to identify new loci that contribute to asthma susceptibility.
METHODS
We leveraged the mixed ancestry of 3902 Latinos and performed an admixture mapping meta-analysis for asthma susceptibility. We replicated associations in an independent study of 3774 Latinos, performed targeted sequencing for fine mapping, and tested for disease correlations with gene expression in the whole blood of more than 500 subjects from 3 racial/ethnic groups.
RESULTS
We identified a genome-wide significant admixture mapping peak at 18q21 in Latinos (P = 6.8 × 10
CONCLUSION
Ancestry at 18q21 was significantly associated with asthma in Latinos and implicated multiple ancestry-informative noncoding variants upstream of SMAD2 with asthma susceptibility. Furthermore, decreased SMAD2 expression in blood was strongly associated with increased asthma risk and increased exacerbations.

Identifiants

DOI: 10.1016/j.jaci.2016.08.057 PMID: 30201514 PMC: PMC6927816
pubmed: 30201514
pii: S0091-6749(18)31274-0
doi: 10.1016/j.jaci.2016.08.057
pmc: PMC6927816
mid: NIHMS1528942
pii:
doi:

Substances chimiques

SMAD2 protein, human 0
Smad2 Protein 0

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

957-969

Subventions

Organisme : NCI NIH HHS
ID : HHSN261200800001E
Pays : United States
Organisme : NCI NIH HHS
ID : R25 CA113710
Pays : United States
Organisme : NCATS NIH HHS
ID : KL2 TR000143
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK113003
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI079139
Pays : United States
Organisme : NHLBI NIH HHS
ID : RC2 HL101651
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL087699
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI077439
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL104608
Pays : United States
Organisme : NHGRI NIH HHS
ID : T32 HG000044
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL079055
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL088133
Pays : United States
Organisme : NHLBI NIH HHS
ID : K23 HL111636
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES015794
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201100037C
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI061774
Pays : United States
Organisme : NCRR NIH HHS
ID : M01 RR000188
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL078885
Pays : United States
Organisme : ARRA NIH HHS
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA113710
Pays : United States
Organisme : NIMHD NIH HHS
ID : P60 MD006902
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK064695
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL132825
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007175
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL118267
Pays : United States

Informations de copyright

Copyright © 2018. Published by Elsevier Inc.

Références

Hum Genet. 2006 Jan;118(5):652-64
pubmed: 16283388
Nature. 2011 Jul 13;475(7355):163-5
pubmed: 21753830
Am J Respir Crit Care Med. 2013 Nov 15;188(10):1202-9
pubmed: 24050698
J Allergy Clin Immunol. 2011 Jul;128(1):37-43.e12
pubmed: 21621256
J Allergy Clin Immunol. 2014 Aug;134(2):295-305
pubmed: 24406073
Nucleic Acids Res. 2002 Jan 1;30(1):207-10
pubmed: 11752295
J Allergy Clin Immunol. 2012 Dec;130(6):1294-301
pubmed: 23040885
Proc Natl Acad Sci U S A. 2010 May 11;107 Suppl 2:8954-61
pubmed: 20445096
J Allergy Clin Immunol. 2012 Jul;130(1):76-82.e12
pubmed: 22502797
J Allergy Clin Immunol. 2015 Jun;135(6):1502-10
pubmed: 25488688
Am J Hum Genet. 2011 May 13;88(5):586-98
pubmed: 21565292
N Engl J Med. 2006 Mar 23;354(12):1264-72
pubmed: 16554528
Am J Hum Genet. 1993 Mar;52(3):506-16
pubmed: 8447318
Bioinformatics. 2012 May 15;28(10):1359-67
pubmed: 22495753
Nat Genet. 2011 Jul 31;43(9):887-92
pubmed: 21804549
N Engl J Med. 2010 Sep 23;363(13):1211-1221
pubmed: 20860503
Hum Biol. 2012 Aug;84(4):343-64
pubmed: 23249312
Trends Genet. 2009 Nov;25(11):489-94
pubmed: 19836853
Biostatistics. 2012 Sep;13(4):762-75
pubmed: 22699862
J Allergy Clin Immunol. 2002 Aug;110(2):249-54
pubmed: 12170265
Proc Natl Acad Sci U S A. 2011 Jul 19;108(29):11983-8
pubmed: 21730125
Carcinogenesis. 2011 Mar;32(3):312-7
pubmed: 21115650
Nature. 2012 Sep 6;489(7414):57-74
pubmed: 22955616
Bioinformatics. 2009 Jun 15;25(12):i213-21
pubmed: 19477991
Genes Immun. 2006 Mar;7(2):95-100
pubmed: 16395390
Proc Natl Acad Sci U S A. 2010 Jan 12;107(2):786-91
pubmed: 20080753
BMC Genomics. 2006 May 16;7:115
pubmed: 16704732
Nature. 2007 Jul 26;448(7152):470-3
pubmed: 17611496
J Allergy Clin Immunol. 2014 Feb;133(2):370-8
pubmed: 23992748
Genome Res. 2002 Jun;12(6):996-1006
pubmed: 12045153
J Allergy Clin Immunol. 2010 Feb;125(2):321-327.e13
pubmed: 19910030
Genomics. 2011 Dec;98(6):422-30
pubmed: 21903159
Hum Genet. 2008 Jun;123(5):455-68
pubmed: 18401594
Am J Respir Crit Care Med. 2004 Feb 1;169(3):386-92
pubmed: 14617512
BMC Syst Biol. 2009 Feb 12;3:19
pubmed: 19216740
Proc Natl Acad Sci U S A. 2006 Sep 19;103(38):14068-73
pubmed: 16945910
Twin Res Hum Genet. 2008 Apr;11(2):132-42
pubmed: 18361713
Am J Hum Genet. 2007 Sep;81(3):559-75
pubmed: 17701901
J Allergy Clin Immunol. 2012 Sep;130(3):622-629.e9
pubmed: 22607992
Curr Protoc Bioinformatics. 2013;43:11.10.1-11.10.33
pubmed: 25431634
PLoS One. 2012;7(8):e42513
pubmed: 22880011
Science. 2015 May 8;348(6235):648-60
pubmed: 25954001
PLoS Genet. 2009 May;5(5):e1000490
pubmed: 19461885
Am J Hum Genet. 2012 Aug 10;91(2):224-37
pubmed: 22863193
Science. 2014 Jun 13;344(6189):1280-5
pubmed: 24926019
J Clin Invest. 2000 Jan;105(1):61-70
pubmed: 10619862
Am J Respir Crit Care Med. 2013 Aug 1;188(3):309-18
pubmed: 23750510

Auteurs

Christopher R Gignoux (CR)

Program in Pharmaceutical Sciences and Pharmacogenomics, University of California, San Francisco, San Francisco, Calif; Department of Bioengineering & Therapeutic Sciences, University of California, San Francisco, San Francisco, Calif. Electronic address: chris.gignoux@ucdenver.edu.

Dara G Torgerson (DG)

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

Maria Pino-Yanes (M)

Department of Medicine, University of California, San Francisco, San Francisco, Calif; CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.

Lawrence H Uricchio (LH)

Department of Bioengineering & Therapeutic Sciences, University of California, San Francisco, San Francisco, Calif.

Joshua Galanter (J)

Department of Bioengineering & Therapeutic Sciences, University of California, San Francisco, San Francisco, Calif; Department of Medicine, University of California, San Francisco, San Francisco, Calif.

Lindsey A Roth (LA)

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

Celeste Eng (C)

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

Donglei Hu (D)

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

Elizabeth A Nguyen (EA)

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

Scott Huntsman (S)

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

Rasika A Mathias (RA)

Department of Medicine, Johns Hopkins University, Baltimore, Md.

Rajesh Kumar (R)

Ann and Robert H. Lurie Children's Hospital of Chicago, Feinberg School of Medicine, Northwestern University, Chicago, Ill.

Jose Rodriguez-Santana (J)

Centro de Neumologia Pediatrica, San Juan, Puerto Rico.

Neeta Thakur (N)

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

Sam S Oh (SS)

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

Meghan McGarry (M)

Department of Pediatrics, University of California, San Francisco, San Francisco, Calif.

Andres Moreno-Estrada (A)

Department of Genetics, Stanford University, Palo Alto, Calif.

Karla Sandoval (K)

Department of Genetics, Stanford University, Palo Alto, Calif.

Cheryl A Winkler (CA)

Molecular Genetics Epidemiology Section, Frederick National Laboratory for Cancer Research, Frederick, Md.

Max A Seibold (MA)

Integrated Center for Genes, Environment, and Health, Department of Pediatrics, Division of Pulmonary and Critical Care Medicine, National Jewish Health, Denver, Colo.

Badri Padhukasahasram (B)

Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, Mich.

David V Conti (DV)

Department of Preventative Medicine, University of Southern California, Los Angeles, Calif.

Harold J Farber (HJ)

Department of Pediatrics, Section of Pulmonology, Baylor College of Medicine and Texas Children's Hospital, Houston, Tex.

Pedro Avila (P)

Division of Allergy-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Ill.

Emerita Brigino-Buenaventura (E)

Department of Allergy & Immunology, Kaiser Permanente-Vallejo Medical Center, Vallejo, Calif.

Michael Lenoir (M)

Bay Area Pediatrics, Oakland, Calif.

Kelley Meade (K)

Children's Hospital and Research Center Oakland, Oakland, Calif.

Denise Serebrisky (D)

Pediatric Pulmonary Division, Jacobi Medical Center, Bronx, NY.

Luisa N Borrell (LN)

Department of Health Sciences, Graduate Program in Public Health, Lehman College, City University of New York, Bronx, NY.

William Rodriguez-Cintron (W)

Veterans Caribbean Health Care System, San Juan, Puerto Rico.

Shannon Thyne (S)

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

Bonnie R Joubert (BR)

National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC.

Isabelle Romieu (I)

Nutritional Epidemiology Group, International Agency for Research on Cancer, Lyon, France.

Albert M Levin (AM)

Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, Mich.

Juan-Jose Sienra-Monge (JJ)

Departmento de Alergia e Inmunologia, Clinica Hospital Infantil de Mexico Federico Gomez, Mexico City, Mexico.

Blanca Estela Del Rio-Navarro (BE)

Departmento de Alergia e Inmunologia, Clinica Hospital Infantil de Mexico Federico Gomez, Mexico City, Mexico.

Weiniu Gan (W)

Division of Lung Diseases, National Heart, Lung, and Blood Institute, Bethesda, Md.

Benjamin A Raby (BA)

Department of Medicine, Harvard Medical School, Boston, Mass.

Scott T Weiss (ST)

Department of Medicine, Harvard Medical School, Boston, Mass.

Eugene Bleecker (E)

Center for Genomics & Personalized Medicine Research, Wake Forest University, Winston-Salem, NC.

Deborah A Meyers (DA)

Center for Genomics & Personalized Medicine Research, Wake Forest University, Winston-Salem, NC.

Fernando J Martinez (FJ)

BIO5 Institute, University of Arizona, Tucson, Ariz.

W James Gauderman (WJ)

Department of Preventative Medicine, University of Southern California, Los Angeles, Calif.

Frank Gilliland (F)

Department of Preventative Medicine, University of Southern California, Los Angeles, Calif.

Stephanie J London (SJ)

National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC.

Carlos D Bustamante (CD)

Department of Genetics, Stanford University, Palo Alto, Calif.

Dan L Nicolae (DL)

Physical Sciences Division, Department of Statistics, University of Chicago, Chicago, Ill.

Carole Ober (C)

Department of Human Genetics, University of Chicago, Chicago, Ill.

Saunak Sen (S)

Department of Preventive Medicine, University of Tennessee Health Sciences Center, Memphis, Tenn.

Kathleen Barnes (K)

Department of Medicine, Johns Hopkins University, Baltimore, Md.

L Keoki Williams (LK)

Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, Mich; Department of Internal Medicine, Henry Ford Health System, Detroit, Mich.

Ryan D Hernandez (RD)

Program in Pharmaceutical Sciences and Pharmacogenomics, University of California, San Francisco, San Francisco, Calif; Department of Bioengineering & Therapeutic Sciences, University of California, San Francisco, San Francisco, Calif.

Esteban G Burchard (EG)

Program in Pharmaceutical Sciences and Pharmacogenomics, University of California, San Francisco, San Francisco, Calif; Department of Bioengineering & Therapeutic Sciences, University of California, San Francisco, San Francisco, Calif; Department of Medicine, University of California, San Francisco, San Francisco, Calif.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Maladies du système immunitaire › Hypersensibilité › Hypersensibilité immédiate › Hypersensibilité respiratoire › Asthme › An admixture mapping meta-analysis implicates...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Cartographie chromosomique › An admixture mapping meta-analysis implicates...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Chromosomes › Chromosomes de mammifère › Chromosomes humains › Chromosomes humains 16-18 › Chromosomes humains de la paire 18 › An admixture mapping meta-analysis implicates...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Prédisposition génétique à une maladie › An admixture mapping meta-analysis implicates...
questionsmedicales.fr › Personnes › Nord-Américains › Groupes de population aux États-Unis › Hispanique ou Latino › An admixture mapping meta-analysis implicates...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › An admixture mapping meta-analysis implicates...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Polymorphisme de nucléotide simple › An admixture mapping meta-analysis implicates...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Protéines Smad › Protéines Smad régulées par les récepteurs › Protéine Smad2 › An admixture mapping meta-analysis implicates...