Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
QIMR Home Page
GenEpi Home Page
Publications
Contacts
Research
Staff Index
Collaborators
Software Tools
Computing Resources
Studies
Search
GenEpi Intranet
PMID
23028483
TITLE
Genome-wide association studies of asthma in population-based cohorts confirm known and suggested loci and identify an additional association near HLA.
ABSTRACT
RATIONALE NlmCategory: BACKGROUND
Asthma has substantial morbidity and mortality and a strong genetic component, but identification of genetic risk factors is limited by availability of suitable studies.
OBJECTIVES NlmCategory: OBJECTIVE
To test if population-based cohorts with self-reported physician-diagnosed asthma and genome-wide association (GWA) data could be used to validate known associations with asthma and identify novel associations.
METHODS NlmCategory: METHODS
The APCAT (Analysis in Population-based Cohorts of Asthma Traits) consortium consists of 1,716 individuals with asthma and 16,888 healthy controls from six European-descent population-based cohorts. We examined associations in APCAT of thirteen variants previously reported as genome-wide significant (P<5 x 10(-8)) and three variants reported as suggestive (P<5× 10(-7)). We also searched for novel associations in APCAT (Stage 1) and followed-up the most promising variants in 4,035 asthmatics and 11,251 healthy controls (Stage 2). Finally, we conducted the first genome-wide screen for interactions with smoking or hay fever.
MAIN RESULTS NlmCategory: RESULTS
We observed association in the same direction for all thirteen previously reported variants and nominally replicated ten of them. One variant that was previously suggestive, rs11071559 in RORA, now reaches genome-wide significance when combined with our data (P = 2.4 × 10(-9)). We also identified two genome-wide significant associations: rs13408661 near IL1RL1/IL18R1 (P(Stage1+Stage2) = 1.1x10(-9)), which is correlated with a variant recently shown to be associated with asthma (rs3771180), and rs9268516 in the HLA region (P(Stage1+Stage2) = 1.1x10(-8)), which appears to be independent of previously reported associations in this locus. Finally, we found no strong evidence for gene-environment interactions with smoking or hay fever status.
CONCLUSIONS NlmCategory: CONCLUSIONS
Population-based cohorts with simple asthma phenotypes represent a valuable and largely untapped resource for genetic studies of asthma.
DATE PUBLISHED
2012
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2012/04/24
accepted 2012/07/27
epublish 2012/09/28
entrez 2012/10/03 06:00
pubmed 2012/10/03 06:00
medline 2013/03/21 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Ramasamy A Ramasamy Adaikalavan A Respiratory Epidemiology and Public Health, Imperial College London, London, United Kingdom.
Kuokkanen M Kuokkanen Mikko M
Vedantam S Vedantam Sailaja S
Gajdos ZK Gajdos Zofia K ZK
Couto Alves A Couto Alves Alexessander A
Lyon HN Lyon Helen N HN
Ferreira MA Ferreira Manuel A R MA
Strachan DP Strachan David P DP
Zhao JH Zhao Jing Hua JH
Abramson MJ Abramson Michael J MJ
Brown MA Brown Matthew A MA
Coin L Coin Lachlan L
Dharmage SC Dharmage Shyamali C SC
Duffy DL Duffy David L DL
Haahtela T Haahtela Tari T
Heath AC Heath Andrew C AC
Janson C Janson Christer C
Kähönen M Kähönen Mika M
Khaw KT Khaw Kay-Tee KT
Laitinen J Laitinen Jaana J
Le Souef P Le Souef Peter P
Lehtimäki T Lehtimäki Terho T
Australian Asthma Genetics Consortium Collaborators
Madden PA Madden Pamela A F PA
Marks GB Marks Guy B GB
Martin NG Martin Nicholas G NG
Matheson MC Matheson Melanie C MC
Palmer CD Palmer Cameron D CD
Palotie A Palotie Aarno A
Pouta A Pouta Anneli A
Robertson CF Robertson Colin F CF
Viikari J Viikari Jorma J
Widen E Widen Elisabeth E
Wjst M Wjst Matthias M
Jarvis DL Jarvis Deborah L DL
Montgomery GW Montgomery Grant W GW
Thompson PJ Thompson Philip J PJ
Wareham N Wareham Nick N
Eriksson J Eriksson Johan J
Jousilahti P Jousilahti Pekka P
Laitinen T Laitinen Tarja T
Pekkanen J Pekkanen Juha J
Raitakari OT Raitakari Olli T OT
O'Connor GT O'Connor George T GT
Salomaa V Salomaa Veikko V
Jarvelin MR Jarvelin Marjo-Riitta MR
Hirschhorn JN Hirschhorn Joel N JN
INVESTIGATORS
JOURNAL
VOLUME: 7
ISSUE: 9
TITLE: PloS one
ISOABBREVIATION: PLoS ONE
YEAR: 2012
MONTH:
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1932-6203
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: PLoS One
COUNTRY: United States
ISSNLINKING: 1932-6203
NLMUNIQUEID: 101285081
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
Cites EMBO Rep. 2001 Jan;2(1):42-8 11252722
Cites Thorax. 2012 Sep;67(9):762-8 22561531
Cites Nat Genet. 2003 Feb;33(2):177-82 12524541
Cites Allergy. 2004 May;59(5):469-78 15080825
Cites Acta Paediatr Scand. 1969;193:Suppl 193:1+ 4911003
Cites Am Rev Respir Dis. 1990 Dec;142(6 Pt 1):1351-8 2252253
Cites Chest. 1991 Jul;100(1):70-5 2060393
Cites Am J Respir Crit Care Med. 1997 Dec;156(6):1773-80 9412554
Cites Eur Respir J. 2005 Sep;26(3):494-502 16135734
Cites Bull World Health Organ. 2005 Jul;83(7):548-54 16175830
Cites Lancet. 2006 Aug 26;368(9537):804-13 16935691
Cites Am J Respir Crit Care Med. 2006 Dec 15;174(12):1299-309 16973978
Cites Eur Respir J. 2007 Mar;29(3):516-21 17215318
Cites Nat Genet. 2007 May;39(5):638-44 17401364
Cites Am J Epidemiol. 2007 Jun 1;165(11):1328-35 17372189
Cites Nature. 2007 Jul 26;448(7152):470-3 17611496
Cites Nat Rev Genet. 2008 May;9(5):356-69 18398418
Cites Am J Respir Crit Care Med. 2008 Jun 1;177(11):1194-200 18310477
Cites Ann Allergy Asthma Immunol. 2008 Jul;101(1):1-8; quiz 8-11, 50 18681077
Cites PLoS Genet. 2008 Aug;4(8):e1000166 18846228
Cites Int J Epidemiol. 2008 Dec;37(6):1220-6 18263651
Cites Nat Genet. 2009 Mar;41(3):342-7 19198610
Cites Nucl Recept Signal. 2009;7:e003 19381306
Cites Am J Hum Genet. 2009 May;84(5):581-93 19426955
Cites Am J Respir Crit Care Med. 2009 Jun 15;179(12):1084-90 19264973
Cites N Engl J Med. 2010 Jan 7;362(1):36-44 20032318
Cites Bioinformatics. 2010 Feb 15;26(4):580-1 20040588
Cites J Allergy Clin Immunol. 2010 Feb;125(2):328-335.e11 20159242
Cites Int J Epidemiol. 2010 Apr;39(2):504-18 19959603
Cites Bioinformatics. 2010 Sep 1;26(17):2190-1 20616382
Cites Curr Opin Allergy Clin Immunol. 2010 Oct;10(5):427-33 20724922
Cites J Allergy Clin Immunol. 2010 Sep;126(3):439-46; quiz 447-8 20816180
Cites N Engl J Med. 2010 Sep 23;363(13):1211-21 20860503
Cites Nature. 2010 Oct 14;467(7317):832-8 20881960
Cites Nat Genet. 2010 Nov;42(11):937-48 20935630
Cites J Allergy Clin Immunol. 2011 Jan;127(1):145-52 21211649
Cites Eur J Hum Genet. 2011 Apr;19(4):458-64 21150878
Cites Genet Epidemiol. 2011 Jul;35(5):310-7 21374718
Cites Respir Res. 2011;12:86 21699702
Cites PLoS Genet. 2011 Jul;7(7):e1002170 21814517
Cites Nat Genet. 2011 Sep;43(9):893-6 21804548
Cites Nat Genet. 2011 Sep;43(9):887-92 21804549
Cites Lancet. 2011 Sep 10;378(9795):1006-14 21907864
Cites Nat Immunol. 2012 Mar;13(3):229-36 22267218
Cites BMJ. 2001 Apr 21;322(7292):949-53 11312225
GRANTS
GRANTID AGENCY COUNTRY
#089062 Wellcome Trust United Kingdom
#5R01HL087679-02 NHLBI NIH HHS United States
1RL1MH083268-01 NIMH NIH HHS United States
G0401527 Medical Research Council United Kingdom
G0901214 Medical Research Council United Kingdom
G1000143 Medical Research Council United Kingdom
K05 AA017688 NIAAA NIH HHS United States
MC_U106179471 Medical Research Council United Kingdom
Department of Health United Kingdom
Intramural NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Asthma genetics
Cohort Studies genetics
Genetic Predisposition to Disease genetics
Genome-Wide Association Study genetics
HLA Antigens genetics
Humans genetics
Middle Aged genetics
Polymorphism, Single Nucleotide genetics
Quantitative Trait Loci genetics
Risk Factors genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 HLA Antigens
OTHER ID's
OTHERID SOURCE
PMC3461045 NLM