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BMC Genetics

, 16:138

Complex traits and quantitative genetics

Abstract

BackgroundPulmonary 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.

ResultsAmong 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, and FEV1-FVC was associated with a genomic region on chromosome 4 upstream of HHIP lowest p-value = 5.94 × 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 DBH p-value = 9.69 × 10 and 19 CYP2A6-7 p-value = 3.49 × 10 and for FEV1-FVC on chromosome 1 TGFB2 p-value = 8.99 × 10, 4 FAM13A p-value = 3.88 × 10, 11 MMP3-12 p-value = 3.29 × 10 and 14 RIN3 p-value = 5.64 × 10.

ConclusionsIn 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.

KeywordsChronic obstructive pulmonary disease DBH FEV1 FEV1-FVC Genome-wide association study Spirometry AbbreviationsCOPDChronic obstructive pulmonary disease

SNPSingle nucleotide polymorphism

MAFMinor allele frequency

AAAfrican American

NHWNon-Hispanic White

FEV1Forced expiratory volume in the first second

FVCForced vital capacity, the total volume of air expired after a maximal inhalation

GWASGenome wide association study

Sharon M. Lutz, Michael H. Cho, John E. Hokanson and Edwin K. Silverman contributed equally to this work.

Electronic supplementary materialThe online version of this article doi:10.1186-s12863-015-0299-4 contains supplementary material, which is available to authorized users.

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Author: Sharon M. Lutz - Michael H. Cho - Kendra Young - Craig P. Hersh - Peter J. Castaldi - Merry-Lynn McDonald - Elizabeth R

Source: https://link.springer.com/



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