A genome-wide association study of COPD identifies a susceptibility locus on chromosome 19q13

Michael H. Cho, Peter J. Castaldi, Emily S. Wan, Mateusz Siedlinski, Craig P. Hersh, Dawn L. Demeo, Blanca E. Himes, Jody S. Sylvia, Barbara J. Klanderman, John P. Ziniti, Christoph Lange, Augusto A. Litonjua, David Sparrow, Elizabeth A. Regan, Barry J. Make, John E. Hokanson, Tanda Murray, Jacqueline B. Hetmanski, Sreekumar G. Pillai, Xiangyang KongWayne H. Anderson, Ruth Tal-Singer, David A. Lomas, Harvey O. Coxson, Lisa D. Edwards, William MacNee, Jørgen Vestbo, Julie C. Yates, Alvar Agusti, Peter M A Calverley, Bartolome Celli, Courtney Crim, Stephen Rennard, Emiel Wouters, Per Bakke, Amund Gulsvik, James D. Crapo, Terri H. Beaty, Edwin K. Silverman

    Research output: Contribution to journalArticlepeer-review


    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 genomewide significant locus on chromosome 19q13 (rs7937, OR = 0.74, P = 2.9 × 10 -9). Genotyping this singlenucleotide 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. © The Author 2011. Published by Oxford University Press. All rights reserved.
    Original languageEnglish
    Article numberddr524
    Pages (from-to)947-957
    Number of pages10
    JournalHuman Molecular Genetics
    Issue number4
    Publication statusPublished - Feb 2012


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