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dc.contributor.authorLutz, Sharon Men_US
dc.contributor.authorCho, Michael Hen_US
dc.contributor.authorYoung, Kendraen_US
dc.contributor.authorHersh, Craig Pen_US
dc.contributor.authorCastaldi, Peter Jen_US
dc.contributor.authorMcDonald, Merry-Lynnen_US
dc.contributor.authorRegan, Elizabethen_US
dc.contributor.authorMattheisen, Manuelen_US
dc.contributor.authorDeMeo, Dawn Len_US
dc.contributor.authorParker, Margareten_US
dc.contributor.authorForeman, Marilynen_US
dc.contributor.authorMake, Barry Jen_US
dc.contributor.authorJensen, Robert Len_US
dc.contributor.authorCasaburi, Richarden_US
dc.contributor.authorLomas, David Aen_US
dc.contributor.authorBhatt, Surya Pen_US
dc.contributor.authorBakke, Peren_US
dc.contributor.authorGulsvik, Amunden_US
dc.contributor.authorCrapo, James Den_US
dc.contributor.authorBeaty, Terri Hen_US
dc.contributor.authorLaird, Nan Men_US
dc.contributor.authorLange, Christophen_US
dc.contributor.authorHokanson, John Een_US
dc.contributor.authorSilverman, Edwin Ken_US
dc.PublishedBMC Genetics. 2015 Dec 03;16(1):138eng
dc.description.abstractBackground Pulmonary function decline is a major contributor to morbidity and mortality among smokers. Post bronchodilator FEV1 and FEV1/FVC ratio are considered the standard assessment of airflow obstruction. We performed a genome-wide association study (GWAS) in 9919 current and former smokers in the COPDGene study (6659 non-Hispanic Whites [NHW] and 3260 African Americans [AA]) to identify associations with spirometric measures (post-bronchodilator FEV1 and FEV1/FVC). We also conducted meta-analysis of FEV1 and FEV1/FVC GWAS in the COPDGene, ECLIPSE, and GenKOLS cohorts (total n = 13,532). Results Among NHW in the COPDGene cohort, both measures of pulmonary function were significantly associated with SNPs at the 15q25 locus [containing CHRNA3/5, AGPHD1, IREB2, CHRNB4] (lowest p-value = 2.17 × 10−11), and FEV1/FVC was associated with a genomic region on chromosome 4 [upstream of HHIP] (lowest p-value = 5.94 × 10−10); both regions have been previously associated with COPD. For the meta-analysis, in addition to confirming associations to the regions near CHRNA3/5 and HHIP, genome-wide significant associations were identified for FEV1 on chromosome 1 [TGFB2] (p-value = 8.99 × 10−9), 9 [DBH] (p-value = 9.69 × 10−9) and 19 [CYP2A6/7] (p-value = 3.49 × 10−8) and for FEV1/FVC on chromosome 1 [TGFB2] (p-value = 8.99 × 10−9), 4 [FAM13A] (p-value = 3.88 × 10−12), 11 [MMP3/12] (p-value = 3.29 × 10−10) and 14 [RIN3] (p-value = 5.64 × 10−9). Conclusions In a large genome-wide association study of lung function in smokers, we found genome-wide significant associations at several previously described loci with lung function or COPD. We additionally identified a novel genome-wide significant locus with FEV1 on chromosome 9 [DBH] in a meta-analysis of three study populations.en_US
dc.publisherBioMed Centraleng
dc.rightsAttribution CC BY 4.0eng
dc.subjectChronic obstructive pulmonary diseaseeng
dc.subjectGenome-wide association studyeng
dc.titleA genome-wide association study identifies risk loci for spirometric measures among smokers of European and African ancestryen_US
dc.typePeer reviewed
dc.typeJournal article
dc.rights.holderCopyright Lutz et al. 2015
dc.subject.nsiVDP::Medisinske Fag: 700en_US

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