A genome-wide association study identifies risk loci for spirometric measures among smokers of European and African ancestry

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A genome-wide association study identifies risk loci for spirometric measures among smokers of European and African ancestry

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Title: A genome-wide association study identifies risk loci for spirometric measures among smokers of European and African ancestry
Author: Lutz, Sharon M.; Cho, Michael H.; Young, Kendra; Hersh, Craig P.; Castaldi, Peter J.; McDonald, Merry-Lynn; Regan, Elizabeth; Mattheisen, Manuel; DeMeo, Dawn L.; Parker, Margaret; Foreman, Marilyn; Make, Barry J.; Jensen, Robert L.; Casaburi, Richard; Lomas, David A.; Bhatt, Surya P.; Bakke, Per; Gulsvik, Amund; Crapo, James D.; Beaty, Terri H.; Laird, Nan M.; Lange, Christoph; Hokanson, John E.; Silverman, Edwin K.

Note: Order does not necessarily reflect citation order of authors.

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.
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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.
Published Version: doi:10.1186/s12863-015-0299-4
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4668640/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:23993693
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