Lutz, Sharon M.Cho, MichaelYoung, KendraHersh, CraigCastaldi, PeterMcDonald, Merry-Lynn NRegan, ElizabethMattheisen, ManuelDemeo, DawnParker, MargaretForeman, MarilynMake, Barry J.Jensen, Robert L.Casaburi, RichardLomas, David A.Bhatt, Surya P.Bakke, PerGulsvik, AmundCrapo, James D.Beaty, Terri H.Laird, NanLange, ChristophHokanson, John E.Silverman, Edwin2016-01-042015Lutz, 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/s12863-015-0299-4.1471-2156http://nrs.harvard.edu/urn-3:HUL.InstRepos:23993693Background: 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-USChronic obstructive pulmonary diseaseDBHFEVGenome-wide association studySpirometryJournal Article2016-01-0410.1186/s12863-015-0299-4