dc.contributor.author | Lutz, Sharon M | en_US |
dc.contributor.author | Cho, Michael H | en_US |
dc.contributor.author | Young, Kendra | en_US |
dc.contributor.author | Hersh, Craig P | en_US |
dc.contributor.author | Castaldi, Peter J | en_US |
dc.contributor.author | McDonald, Merry-Lynn | en_US |
dc.contributor.author | Regan, Elizabeth | en_US |
dc.contributor.author | Mattheisen, Manuel | en_US |
dc.contributor.author | DeMeo, Dawn L | en_US |
dc.contributor.author | Parker, Margaret | en_US |
dc.contributor.author | Foreman, Marilyn | en_US |
dc.contributor.author | Make, Barry J | en_US |
dc.contributor.author | Jensen, Robert L | en_US |
dc.contributor.author | Casaburi, Richard | en_US |
dc.contributor.author | Lomas, David A | en_US |
dc.contributor.author | Bhatt, Surya P | en_US |
dc.contributor.author | Bakke, Per | en_US |
dc.contributor.author | Gulsvik, Amund | en_US |
dc.contributor.author | Crapo, James D | en_US |
dc.contributor.author | Beaty, Terri H | en_US |
dc.contributor.author | Laird, Nan M | en_US |
dc.contributor.author | Lange, Christoph | en_US |
dc.contributor.author | Hokanson, John E | en_US |
dc.contributor.author | Silverman, Edwin K | en_US |
dc.date.accessioned | 2016-06-28T09:54:46Z | |
dc.date.available | 2016-06-28T09:54:46Z | |
dc.date.issued | 2015-12-03 | |
dc.Published | BMC Genetics. 2015 Dec 03;16(1):138 | eng |
dc.identifier.uri | https://hdl.handle.net/1956/12199 | |
dc.description.abstract | Background 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.language.iso | eng | eng |
dc.publisher | BioMed Central | eng |
dc.rights | Attribution CC BY 4.0 | eng |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0 | eng |
dc.subject | Chronic obstructive pulmonary disease | eng |
dc.subject | DBH | eng |
dc.subject | FEV1 | eng |
dc.subject | FEV1/FVC | eng |
dc.subject | Genome-wide association study | eng |
dc.subject | Spirometry | eng |
dc.title | A genome-wide association study identifies risk loci for spirometric measures among smokers of European and African ancestry | en_US |
dc.type | Peer reviewed | |
dc.type | Journal article | |
dc.date.updated | 2016-02-25T14:29:14Z | |
dc.description.version | publishedVersion | en_US |
dc.rights.holder | Copyright Lutz et al. 2015 | |
dc.identifier.doi | https://doi.org/10.1186/s12863-015-0299-4 | |
dc.subject.nsi | VDP::Medisinske Fag: 700 | en_US |