The Association of Genome-Wide Significant Spirometric Loci with Chronic Obstructive Pulmonary Disease Susceptibility
Year: 2011
Type: article
Study design: Observational Study
Abstract: Two recent metaanalyses of genome-wide association studies conducted by the CHARGE and SpiroMeta consortia identified novel loci yielding evidence of association at or near genome-wide significance (GWS) with FEV(1) and FEV(1)/FVC. We hypothesized that a subset of these markers would also be associated with chronic obstructive pulmonary disease (COPD) susceptibility. Thirty-two single-nucleotide polymorphisms (SNPs) in or near 17 genes in 11 previously identified GWS spirometric genomic regions were tested for association with COPD status in four COPD case-control study samples (NETT/NAS, the Norway case-control study, ECLIPSE, and the first 1,000 subjects in COPDGene; total sample size, 3,456 cases and 1,906 controls). In addition to testing the 32 spirometric GWS SNPs, we tested a dense panel of imputed HapMap2 SNP markers from the 17 genes located near the 32 GWS SNPs and in a set of 21 well studied COPD candidate genes. Of the previously identified GWS spirometric genomic regions, three loci harbored SNPs associated with COPD susceptibility at a 5% false discovery rate: the 4q24 locus including FLJ20184/INTS12/GSTCD/NPNT, the 6p21 locus including AGER and PPT2, and the 5q33 locus including ADAM19. In conclusion, markers previously associated at or near GWS with spirometric measures were tested for association with COPD status in data from four COPD case-control studies, and three loci showed evidence of association with COPD susceptibility at a 5% false discovery rate.
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: U.S. Department of Veterans Affairs, AstraZeneca, GlaxoSmithKline, Brigham and Women's Hospital, University of Minnesota, Johns Hopkins University, University of Pittsburgh, COPD Foundation, Temple University, National Jewish Health, Morehouse School of Medicine, National Institutes of Health, Agency for Healthcare Research and Quality, Centers for Medicare and Medicaid Services, University of California, San Diego, University of Texas Health Science Center at San Antonio, National Heart, Lung, and Blood Institute, National Center for Research Resources, National Center for Advancing Translational Sciences
Awards: Predictive Modeling with Clinical and Genomic Data in COPD, G2683389281, Genetic Determinants of COPD in Diverse Ethnic Groups, Fine Mapping of COPD Susceptibility Genes, G5258357286, (2 of 2) Genetic Epidemiology of COPD, Tufts Clinical and Translation Science Institute (UL1), Atlanta Clinical and Translational Science Institute (ACTSI) Renewal, G6160285194, (1 of 2) Genetic Epidemiology of COPD, G754838926, Approaches to Identify Rare and Common Genetic Determinants in Severe COPD, Common Genetic Determinants of Asthma and COPD-PROGRAM PROJECT, G794209665, G7949433598, G8354759825, G9000091268, G9000228787
OpenAlex ID: W2040421689