期刊
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
卷 45, 期 6, 页码 1147-1153出版社
AMER THORACIC SOC
DOI: 10.1165/rcmb.2011-0055OC
关键词
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资金
- National Institutes of Health (NIH) [R01 HL075478, R01 HL084323, P01 HL083069, U01 HL089856, K08HL102265, UL1 RR025752, U01 HL089897]
- National Heart, Lung, and Blood Institute
- Centers for Medicare and Medicaid Services
- Agency for Healthcare Research and Quality
- ERIC of the US Department of Veterans Affairs
- Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC)
- GlaxoSmithKline
- COPD Foundation
- Astra-Zeneca
- MRC [G0901786] Funding Source: UKRI
- Medical Research Council [G0901786] Funding Source: researchfish
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 FEV1 and FEV1/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 32GWS 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.
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