A genome-wide association study of COPD identifies a susceptibility locus on chromosome 19q13
| Autor: | Blanca E. Himes, David A. Lomas, Barbara J. Klanderman, Dawn L. DeMeo, Craig P. Hersh, William MacNee, Elizabeth A. Regan, John E. Hokanson, Emily S. Wan, John Ziniti, Christoph Lange, Courtney Crim, Julie C. Yates, David Sparrow, Jacqueline B. Hetmanski, Alvar Agusti, Peter J. Castaldi, Lisa D. Edwards, Sreekumar G. Pillai, Bartolome R. Celli, Edwin K. Silverman, Jørgen Vestbo, Barry J. Make, Per Bakke, Mateusz Siedlinski, Peter M.A. Calverley, Terri H. Beaty, Xiangyang Kong, Michael H. Cho, Stephen I. Rennard, Tanda Murray, James D. Crapo, Wayne H. Anderson, Augusto A. Litonjua, Harvey O. Coxson, Emiel F.M. Wouters, Ruth Tal-Singer, Jody S. Sylvia, Amund Gulsvik |
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| Přispěvatelé: | Pulmonologie, RS: NUTRIM - R3 - Chronic inflammatory disease and wasting |
| Rok vydání: | 2011 |
| Předmět: |
Genetics
Chronic bronchitis Linkage disequilibrium Genotyping Techniques Association Studies Articles Single-nucleotide polymorphism Genome-wide association study General Medicine Biology Pulmonary Disease Chronic Obstructive Genetic epidemiology Humans Genetic Predisposition to Disease 1000 Genomes Project Chromosomes Human Pair 19 Molecular Biology Genotyping Genetics (clinical) Follow-Up Studies Genome-Wide Association Study Genetic association |
| Zdroj: | Human Molecular Genetics, 21(4), 947-957. Oxford University Press |
| ISSN: | 1460-2083 0964-6906 |
| Popis: | The genetic risk factors for chronic obstructive pulmonary disease (COPD) are still largely unknown. To date, genome-wide association studies (GWASs) of limited size have identified several novel risk loci for COPD at CHRNA3/CHRNA5/IREB2, HHIP and FAM13A; additional loci may be identified through larger studies. We performed a GWAS using a total of 3499 cases and 1922 control subjects from four cohorts: the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE); the Normative Aging Study (NAS) and National Emphysema Treatment Trial (NETT); Bergen, Norway (GenKOLS); and the COPDGene study. Genotyping was performed on Illumina platforms with additional markers imputed using 1000 Genomes data; results were summarized using fixed-effect meta-analysis. We identified a new genome-wide significant locus on chromosome 19q13 (rs7937, OR = 0.74, P = 2.9 x 10(-9)). Genotyping this single nucleotide polymorphism (SNP) and another nearby SNP in linkage disequilibrium (rs2604894) in 2859 subjects from the family-based International COPD Genetics Network study (ICGN) demonstrated supportive evidence for association for COPD (P = 0.28 and 0.11 for rs7937 and rs2604894), pre-bronchodilator FEV(1) (P = 0.08 and 0.04) and severe (GOLD 3&4) COPD (P = 0.09 and 0.017). This region includes RAB4B, EGLN2, MIA and CYP2A6, and has previously been identified in association with cigarette smoking behavior. |
| Databáze: | OpenAIRE |
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