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

M.H. Cho; P.J. Castaldi; E.S. Wan; M. Siedlinski; C.P. Hersh; D.L. Demeo; B.E. Himes; J.S. Sylvia; B.J. Klanderman; J.P. Ziniti; C. Lange; A.A. Litonjua; D. Sparrow; E.A. Regan; B.J. Make; J.E. Hokanson; T. Murray; J.B. Hetmanski; S.G. Pillai; X. Kong; W.H. Anderson; R. Tal Singer; D.A. Lomas; H.O. Coxson; L.D. Edwards; W. MacNee; J. Vestbo; J.C. Yates; A. Agusti; P.M. Calverley; B. Celli; C. Crim; S. Rennard; E.F.M. Wouters; P. Bakke; A. Gulsvik; J.D. Crapo; T.H. Beaty; E.K. Silverman

doi:10.1093/hmg/ddr524

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

M.H. Cho^*, P.J. Castaldi, E.S. Wan, M. Siedlinski, C.P. Hersh, D.L. Demeo, B.E. Himes, J.S. Sylvia, B.J. Klanderman, J.P. Ziniti, C. Lange, A.A. Litonjua, D. Sparrow, E.A. Regan, B.J. Make, J.E. Hokanson, T. Murray, J.B. Hetmanski, S.G. Pillai, X. KongW.H. Anderson, R. Tal Singer, D.A. Lomas, H.O. Coxson, L.D. Edwards, W. MacNee, J. Vestbo, J.C. Yates, A. Agusti, P.M. Calverley, B. Celli, C. Crim, S. Rennard, E.F.M. Wouters, P. Bakke, A. Gulsvik, J.D. Crapo, T.H. Beaty, E.K. Silverman

^*Corresponding author for this work

Pulmonologie

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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.

Original language	English
Pages (from-to)	947-957
Journal	Human Molecular Genetics
Volume	21
Issue number	4
DOIs	https://doi.org/10.1093/hmg/ddr524
Publication status	Published - 1 Jan 2012

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10.1093/hmg/ddr524

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Cho, M. H., Castaldi, P. J., Wan, E. S., Siedlinski, M., Hersh, C. P., Demeo, D. L., Himes, B. E., Sylvia, J. S., Klanderman, B. J., Ziniti, J. P., Lange, C., Litonjua, A. A., Sparrow, D., Regan, E. A., Make, B. J., Hokanson, J. E., Murray, T., Hetmanski, J. B., Pillai, S. G., ... Silverman, E. K. (2012). A genome-wide association study of COPD identifies a susceptibility locus on chromosome 19q13. Human Molecular Genetics, 21(4), 947-957. https://doi.org/10.1093/hmg/ddr524

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title = "A genome-wide association study of COPD identifies a susceptibility locus on chromosome 19q13.",

abstract = "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.",

author = "M.H. Cho and P.J. Castaldi and E.S. Wan and M. Siedlinski and C.P. Hersh and D.L. Demeo and B.E. Himes and J.S. Sylvia and B.J. Klanderman and J.P. Ziniti and C. Lange and A.A. Litonjua and D. Sparrow and E.A. Regan and B.J. Make and J.E. Hokanson and T. Murray and J.B. Hetmanski and S.G. Pillai and X. Kong and W.H. Anderson and {Tal Singer}, R. and D.A. Lomas and H.O. Coxson and L.D. Edwards and W. MacNee and J. Vestbo and J.C. Yates and A. Agusti and P.M. Calverley and B. Celli and C. Crim and S. Rennard and E.F.M. Wouters and P. Bakke and A. Gulsvik and J.D. Crapo and T.H. Beaty and E.K. Silverman",

year = "2012",

month = jan,

day = "1",

doi = "10.1093/hmg/ddr524",

language = "English",

volume = "21",

pages = "947--957",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "4",

}

Cho, MH, Castaldi, PJ, Wan, ES, Siedlinski, M, Hersh, CP, Demeo, DL, Himes, BE, Sylvia, JS, Klanderman, BJ, Ziniti, JP, Lange, C, Litonjua, AA, Sparrow, D, Regan, EA, Make, BJ, Hokanson, JE, Murray, T, Hetmanski, JB, Pillai, SG, Kong, X, Anderson, WH, Tal Singer, R, Lomas, DA, Coxson, HO, Edwards, LD, MacNee, W, Vestbo, J, Yates, JC, Agusti, A, Calverley, PM, Celli, B, Crim, C, Rennard, S, Wouters, EFM, Bakke, P, Gulsvik, A, Crapo, JD, Beaty, TH & Silverman, EK 2012, 'A genome-wide association study of COPD identifies a susceptibility locus on chromosome 19q13.', Human Molecular Genetics, vol. 21, no. 4, pp. 947-957. https://doi.org/10.1093/hmg/ddr524

TY - JOUR

T1 - A genome-wide association study of COPD identifies a susceptibility locus on chromosome 19q13.

AU - Cho, M.H.

AU - Castaldi, P.J.

AU - Wan, E.S.

AU - Siedlinski, M.

AU - Hersh, C.P.

AU - Demeo, D.L.

AU - Himes, B.E.

AU - Sylvia, J.S.

AU - Klanderman, B.J.

AU - Ziniti, J.P.

AU - Lange, C.

AU - Litonjua, A.A.

AU - Sparrow, D.

AU - Regan, E.A.

AU - Make, B.J.

AU - Hokanson, J.E.

AU - Murray, T.

AU - Hetmanski, J.B.

AU - Pillai, S.G.

AU - Kong, X.

AU - Anderson, W.H.

AU - Tal Singer, R.

AU - Lomas, D.A.

AU - Coxson, H.O.

AU - Edwards, L.D.

AU - MacNee, W.

AU - Vestbo, J.

AU - Yates, J.C.

AU - Agusti, A.

AU - Calverley, P.M.

AU - Celli, B.

AU - Crim, C.

AU - Rennard, S.

AU - Wouters, E.F.M.

AU - Bakke, P.

AU - Gulsvik, A.

AU - Crapo, J.D.

AU - Beaty, T.H.

AU - Silverman, E.K.

PY - 2012/1/1

Y1 - 2012/1/1

N2 - 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.

AB - 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.

U2 - 10.1093/hmg/ddr524

DO - 10.1093/hmg/ddr524

M3 - Article

C2 - 22080838

SN - 0964-6906

VL - 21

SP - 947

EP - 957

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 4

ER -