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 | 2016-01-04T19:25:36Z | |
dc.date.issued | 2015 | en_US |
dc.identifier.citation | Lutz, S. M., M. H. Cho, K. Young, C. P. Hersh, P. J. Castaldi, M. McDonald, E. Regan, et al. 2015. “A genome-wide association study identifies risk loci for spirometric measures among smokers of European and African ancestry.” BMC Genetics 16 (1): 138. doi:10.1186/s12863-015-0299-4. http://dx.doi.org/10.1186/s12863-015-0299-4. | en |
dc.identifier.issn | 1471-2156 | en |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:23993693 | |
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. Electronic supplementary material The online version of this article (doi:10.1186/s12863-015-0299-4) contains supplementary material, which is available to authorized users. | en |
dc.language.iso | en_US | en |
dc.publisher | BioMed Central | en |
dc.relation.isversionof | doi:10.1186/s12863-015-0299-4 | en |
dc.relation.hasversion | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4668640/pdf/ | en |
dash.license | LAA | en_US |
dc.subject | Chronic obstructive pulmonary disease | en |
dc.subject | DBH | en |
dc.subject | FEV | en |
dc.subject | Genome-wide association study | en |
dc.subject | Spirometry | en |
dc.title | A genome-wide association study identifies risk loci for spirometric measures among smokers of European and African ancestry | en |
dc.type | Journal Article | en_US |
dc.description.version | Version of Record | en |
dc.relation.journal | BMC Genetics | en |
dash.depositing.author | Cho, Michael H. | en_US |
dc.date.available | 2016-01-04T19:25:36Z | |
dc.identifier.doi | 10.1186/s12863-015-0299-4 | * |
dash.authorsordered | false | |
dash.contributor.affiliated | McDonald, Merry-Lynn N | |
dash.contributor.affiliated | Lange, Christoph | |
dash.contributor.affiliated | Castaldi, Peter | |
dash.contributor.affiliated | Hersh, Craig | |
dash.contributor.affiliated | Laird, Nan | |
dash.contributor.affiliated | Demeo, Dawn | |
dash.contributor.affiliated | Silverman, Edwin | |
dash.contributor.affiliated | Cho, Michael | |