A large-scale, consortium-based genomewide association study of asthma

The New England Journal of Medicine
Miriam F MoffattGABRIEL Consortium

Abstract

Susceptibility to asthma is influenced by genes and environment; implicated genes may indicate pathways for therapeutic intervention. Genetic risk factors may be useful in identifying subtypes of asthma and determining whether intermediate phenotypes, such as elevation of the total serum IgE level, are causally linked to disease. We carried out a genomewide association study by genotyping 10,365 persons with physician-diagnosed asthma and 16,110 unaffected persons, all of whom were matched for ancestry. We used random-effects pooled analysis to test for association in the overall study population and in subgroups of subjects with childhood-onset asthma (defined as asthma developing before 16 years of age), later-onset asthma, severe asthma, and occupational asthma. We observed associations of genomewide significance between asthma and the following single-nucleotide polymorphisms: rs3771166 on chromosome 2, implicating IL1RL1/IL18R1 (P=3×10(−9)); rs9273349 on chromosome 6, implicating HLA-DQ (P=7×10(−14)); rs1342326 on chromosome 9, flanking IL33 (P=9×10(−10)); rs744910 on chromosome 15 in SMAD3 (P=4×10(−9)); and rs2284033 on chromosome 22 in IL2RB (P=1.1×10(−8)). Association with the ORMDL3/GSDMB locus on chromosome 17q21 was ...Continue Reading

References

Apr 17, 2013·Seminars in Immunopathology·Arthur KaserRichard S Blumberg
May 15, 2013·Human Genetics·David B KantorJoel N Hirschhorn
Feb 22, 2012·European Journal of Epidemiology·Liesbeth Duijts
Jul 28, 2011·Current Allergy and Asthma Reports·Jeroen DouwesNeil Pearce
Dec 6, 2012·Current Allergy and Asthma Reports·Samuel J Wadsworth, Andrew J Sandford
Feb 6, 2013·Current Allergy and Asthma Reports·Barbara Rogala, Joanna Glück
Apr 16, 2011·Clinical Reviews in Allergy & Immunology·Carlo Selmi
Aug 15, 2012·Journal of Molecular Neuroscience : MN·Yue PanLong-Yang Wu
Sep 17, 2013·Trends in Immunology·Julie DeckersHamida Hammad
Sep 18, 2013·Lancet·Fernando D Martinez, Donata Vercelli
Jan 17, 2014·The Lancet. Respiratory Medicine·Daniel W BelskyAvshalom Caspi
Jan 17, 2014·The Lancet. Respiratory Medicine·Oliver Fuchs, Erika von Mutius
Mar 14, 2014·The Lancet. Respiratory Medicine·Heidi MakriniotiS L Johnston
Feb 20, 2013·Cell Research·Bart N Lambrecht, Hamida Hammad
Mar 16, 2012·European Journal of Human Genetics : EJHG·Lisbeth Venø KruseAnders Dupont Børglum
Feb 28, 2013·European Journal of Human Genetics : EJHG·Anne-Marie MadoreCatherine Laprise
Dec 27, 2011·Nature Genetics·Lavinia PaternosterEArly Genetics & Lifecourse Epidemiology (EAGLE) Consortium
Jun 4, 2013·Nature Genetics·David EllinghausStephan Weidinger
Jan 24, 2012·Nature Immunology·See Heng WongAndrew N J McKenzie
Jan 22, 2013·Nature Immunology·Andrew C Chan, Timothy W Behrens
May 9, 2012·Nature Medicine·Stephen T Holgate
Aug 8, 2013·Nature Medicine·Guy G BrusselleKen R Bracke
Aug 3, 2011·Nature Reviews. Rheumatology·Gillian M BellJohn D Isaacs
Jan 7, 2011·The New England Journal of Medicine·Dana B HancockCHARGE Pulmonary Function Working Group
Sep 6, 2013·The New England Journal of Medicine·Bruce D Levy
Feb 25, 2011·The New England Journal of Medicine·Markus J EgeGABRIELA Transregio 22 Study Group
Mar 29, 2013·The New England Journal of Medicine·Minal CalışkanCarole Ober
Feb 7, 2012·Proceedings of the National Academy of Sciences of the United States of America·Emma LefrançaisCorinne Cayrol
Sep 27, 2012·Proceedings of the National Academy of Sciences of the United States of America·Marina MillerDavid H Broide
Feb 19, 2011·The Journal of Biological Chemistry·Andrea L MaratPeter S McPherson
Sep 13, 2012·Pediatric Allergy, Immunology, and Pulmonology·Elizabeth A Nguyen, Esteban G Burchard
Feb 3, 2012·Bioinformatics·Clara S Tang, Manuel A R Ferreira
Jun 28, 2012·International Journal of Epidemiology·Claudia E KuehniSwiss Paediatric Oncology Group (SPOG)
Jan 31, 2012·Journal of the National Cancer Institute·Kevin Y UrayamaJames D McKay

Citations

Dec 1, 1990·The American Review of Respiratory Disease·David L DuffyJ D Mathews
Dec 24, 1981·The New England Journal of Medicine·D G MarshW B Bias
Apr 1, 1997·Human Molecular Genetics·Miriam F Moffatt, William O C M Cookson
Oct 6, 1997·American Journal of Respiratory and Critical Care Medicine·D H SmithW B Saunders
Dec 22, 1999·The Journal of Immunology : Official Journal of the American Association of Immunologists·T FukaoS Koyasu
Jan 4, 2001·The New England Journal of Medicine·A B Kay
May 30, 2001·European Journal of Human Genetics : EJHG·Miriam F MoffattWilliam O C M Cookson
Sep 7, 2001·Nature Genetics·A J WalleyWilliam O C M Cookson
Jul 12, 2002·Nature·Paul Van EerdeweghTim P Keith
Oct 21, 2003·Nature Genetics·Maxine AllenWilliam O C M Cookson
Dec 23, 2006·Proceedings of the National Academy of Sciences of the United States of America·Virginie CarriereJean-Philippe Girard
Mar 30, 2007·The European Respiratory Journal·A K KonstantinidisJohn W Holloway
Jun 19, 2007·American Journal of Respiratory and Critical Care Medicine·Gudrun WeinmayrISAAC Phase Two Study Group
Dec 12, 2007·International Journal of Biological Sciences·Minna AnthoniHenrik J Wolff
Feb 27, 2008·Genetic Epidemiology·Frank Dudbridge, Arief Gusnanto
Mar 18, 2008·Human Molecular Genetics·Julia H WhiteSreekumar G Pillai
Apr 12, 2008·The New England Journal of Medicine·Carole OberGeoffrey L Chupp
Jul 16, 2008·The Journal of Allergy and Clinical Immunology·Donata Vercelli
Aug 30, 2008·PLoS Medicine·Nuala A SheehanMartin D Tobin
Oct 17, 2008·The New England Journal of Medicine·Emmanuelle BouzigonFlorence Demenais
Dec 17, 2008·Inflammation & Allergy Drug Targets·Kayhan T Nouri-Aria, Stephen R Durham
Feb 10, 2009·Nature Genetics·Daniel F GudbjartssonKari Stefansson
Feb 19, 2009·Nature Reviews. Genetics·William O C M CooksonMark Lathrop
Apr 8, 2009·The Journal of Allergy and Clinical Immunology·Sven LétourneauOnur Boyman
May 12, 2009·American Journal of Human Genetics·Blanca E HimesScott T Weiss
Jul 1, 2009·British Journal of Pharmacology·Graeme F Nixon
Jul 2, 2009·JAMA : the Journal of the American Medical Association·Paul ElliottJaspal S Kooner
Sep 5, 2009·American Journal of Respiratory and Critical Care Medicine·Gerard H KoppelmanDirkje S Postma
Dec 17, 2009·Nature Genetics·Emmanouela RepapiMartin D Tobin
Dec 25, 2009·The New England Journal of Medicine·Patrick SleimanHakon Hakonarson
Feb 26, 2010·Nature·David K BreslowJonathan S Weissman

Related Concepts

Genome-Wide Association Study
Biochemical Pathway
Immune System
ORMDL3 gene
Human Leukocyte Antigen DQ (Lab Test)
Chromosomes, Human, Pair 6
GSDMB
IL18R1 gene
Logistic Regression
Chromosomes, Human

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