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

ABSTRACT: 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).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)).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.

SUBMITTER: Lutz SM 

PROVIDER: S-EPMC4668640 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature