Vis enkel innførsel

dc.contributor.authorPillai, Sreekumar G.en_US
dc.contributor.authorGe, Dongliangen_US
dc.contributor.authorZhu, Guohuaen_US
dc.contributor.authorKong, Xiangyangen_US
dc.contributor.authorShianna, Kevin V.en_US
dc.contributor.authorNeed, Anna C.en_US
dc.contributor.authorFeng, Shengen_US
dc.contributor.authorHersh, Craig P.en_US
dc.contributor.authorBakke, Per S.en_US
dc.contributor.authorGulsvik, Amunden_US
dc.contributor.authorRuppert, Andreasen_US
dc.contributor.authorCarlsen, Karin Cecilie Lødrupen_US
dc.contributor.authorRoses, Allenen_US
dc.contributor.authorAnderson, Wayneen_US
dc.contributor.authorRennard, Stephen I.en_US
dc.contributor.authorLomas, David A.en_US
dc.contributor.authorSilverman, Edwin K.en_US
dc.contributor.authorGoldstein, David B.en_US
dc.date.accessioned2016-08-05T06:33:46Z
dc.date.available2016-08-05T06:33:46Z
dc.date.issued2009-03-20
dc.PublishedPLoS Genetics 2009, 5(3):e1000421eng
dc.identifier.issn1553-7404
dc.identifier.urihttps://hdl.handle.net/1956/12450
dc.description.abstractThere is considerable variability in the susceptibility of smokers to develop chronic obstructive pulmonary disease (COPD). The only known genetic risk factor is severe deficiency of α1-antitrypsin, which is present in 1–2% of individuals with COPD. We conducted a genome-wide association study (GWAS) in a homogenous case-control cohort from Bergen, Norway (823 COPD cases and 810 smoking controls) and evaluated the top 100 single nucleotide polymorphisms (SNPs) in the family-based International COPD Genetics Network (ICGN; 1891 Caucasian individuals from 606 pedigrees) study. The polymorphisms that showed replication were further evaluated in 389 subjects from the US National Emphysema Treatment Trial (NETT) and 472 controls from the Normative Aging Study (NAS) and then in a fourth cohort of 949 individuals from 127 extended pedigrees from the Boston Early-Onset COPD population. Logistic regression models with adjustments of covariates were used to analyze the case-control populations. Family-based association analyses were conducted for a diagnosis of COPD and lung function in the family populations. Two SNPs at the α-nicotinic acetylcholine receptor (CHRNA 3/5) locus were identified in the genome-wide association study. They showed unambiguous replication in the ICGN family-based analysis and in the NETT case-control analysis with combined p-values of 1.48×10−10, (rs8034191) and 5.74×10−10 (rs1051730). Furthermore, these SNPs were significantly associated with lung function in both the ICGN and Boston Early-Onset COPD populations. The C allele of the rs8034191 SNP was estimated to have a population attributable risk for COPD of 12.2%. The association of hedgehog interacting protein (HHIP) locus on chromosome 4 was also consistently replicated, but did not reach genome-wide significance levels. Genome-wide significant association of the HHIP locus with lung function was identified in the Framingham Heart study (Wilk et al., companion article in this issue of PLoS Genetics; doi:10.1371/journal.pgen.1000429). The CHRNA 3/5 and the HHIP loci make a significant contribution to the risk of COPD. CHRNA3/5 is the same locus that has been implicated in the risk of lung cancer.en_US
dc.language.isoengeng
dc.publisherPLoSeng
dc.rightsAttribution CC BYeng
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/eng
dc.titleA genome-wide association study in chronic obstructive pulmonary disease (COPD): Identification of two major susceptibility locien_US
dc.typePeer reviewed
dc.typeJournal article
dc.date.updated2016-04-08T08:15:56Z
dc.description.versionpublishedVersionen_US
dc.rights.holderCopyright 2009 Pillai et al
dc.identifier.doihttps://doi.org/10.1371/journal.pgen.1000421
dc.identifier.cristin346287
dc.subject.nsiVDP::Medisinske fag: 700::Klinisk medisinske fag: 750::Lungesykdommer: 777
dc.subject.nsiVDP::Midical sciences: 700::Clinical medical sciences: 750::Lung diseases: 777
dc.subject.nsiVDP::Medisinske fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk genetikk: 714
dc.subject.nsiVDP::Midical sciences: 700::Basic medical, dental and veterinary sciences: 710::Medical genetics: 714


Tilhørende fil(er)

Thumbnail

Denne innførselen finnes i følgende samling(er)

Vis enkel innførsel

Attribution CC BY
Med mindre annet er angitt, så er denne innførselen lisensiert som Attribution CC BY