Show simple item record

dc.contributor.authorLutz, Sharon M.en_US
dc.contributor.authorCho, Michael H.en_US
dc.contributor.authorYoung, Kendraen_US
dc.contributor.authorHersh, Craig P.en_US
dc.contributor.authorCastaldi, Peter J.en_US
dc.contributor.authorMcDonald, Merry-Lynnen_US
dc.contributor.authorRegan, Elizabethen_US
dc.contributor.authorMattheisen, Manuelen_US
dc.contributor.authorDeMeo, Dawn L.en_US
dc.contributor.authorParker, Margareten_US
dc.contributor.authorForeman, Marilynen_US
dc.contributor.authorMake, Barry J.en_US
dc.contributor.authorJensen, Robert L.en_US
dc.contributor.authorCasaburi, Richarden_US
dc.contributor.authorLomas, David A.en_US
dc.contributor.authorBhatt, Surya P.en_US
dc.contributor.authorBakke, Peren_US
dc.contributor.authorGulsvik, Amunden_US
dc.contributor.authorCrapo, James D.en_US
dc.contributor.authorBeaty, Terri H.en_US
dc.contributor.authorLaird, Nan M.en_US
dc.contributor.authorLange, Christophen_US
dc.contributor.authorHokanson, John E.en_US
dc.contributor.authorSilverman, Edwin K.en_US
dc.date.accessioned2016-01-04T19:25:36Z
dc.date.issued2015en_US
dc.identifier.citationLutz, 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.issn1471-2156en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:23993693
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. 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.isoen_USen
dc.publisherBioMed Centralen
dc.relation.isversionofdoi:10.1186/s12863-015-0299-4en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4668640/pdf/en
dash.licenseLAAen_US
dc.subjectChronic obstructive pulmonary diseaseen
dc.subjectDBHen
dc.subjectFEVen
dc.subjectGenome-wide association studyen
dc.subjectSpirometryen
dc.titleA genome-wide association study identifies risk loci for spirometric measures among smokers of European and African ancestryen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalBMC Geneticsen
dash.depositing.authorCho, Michael H.en_US
dc.date.available2016-01-04T19:25:36Z
dc.identifier.doi10.1186/s12863-015-0299-4*
dash.authorsorderedfalse
dash.contributor.affiliatedMcDonald, Merry-Lynn N
dash.contributor.affiliatedCastaldi, Peter
dash.contributor.affiliatedHersh, Craig
dash.contributor.affiliatedLange, Christoph
dash.contributor.affiliatedCho, Michael
dash.contributor.affiliatedDemeo, Dawn
dash.contributor.affiliatedLaird, Nan
dash.contributor.affiliatedSilverman, Edwin


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record