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 Kong; Wayne 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; ICGN Investigators

doi:10.1093/hmg/ddr524

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, ICGN Investigators

211 Citations (Scopus)

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 × 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
Journal	Human Molecular Genetics
Volume	21
Issue number	4
Pages (from-to)	947-57
Number of pages	11
ISSN	0964-6906
DOIs	https://doi.org/10.1093/hmg/ddr524
Publication status	Published - 2012

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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., ... ICGN Investigators (2012). A genome-wide association study of COPD identifies a susceptibility locus on chromosome 19q13. Human Molecular Genetics, 21(4), 947-57. https://doi.org/10.1093/hmg/ddr524

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, PMA, Celli, B, Crim, C, Rennard, S, Wouters, E, Bakke, P, Gulsvik, A, Crapo, JD, Beaty, TH, Silverman, EK & ICGN Investigators 2012, 'A genome-wide association study of COPD identifies a susceptibility locus on chromosome 19q13', Human Molecular Genetics, vol. 21, no. 4, pp. 947-57. https://doi.org/10.1093/hmg/ddr524

@article{db933c77af2246498eb18da01fb05907,

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

year = "2012",

doi = "10.1093/hmg/ddr524",

language = "English",

volume = "21",

pages = "947--57",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "4",

}

TY - JOUR

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

AU - Cho, Michael H

AU - Castaldi, Peter J

AU - Wan, Emily S

AU - Siedlinski, Mateusz

AU - Hersh, Craig P

AU - Demeo, Dawn L

AU - Himes, Blanca E

AU - Sylvia, Jody S

AU - Klanderman, Barbara J

AU - Ziniti, John P

AU - Lange, Christoph

AU - Litonjua, Augusto A

AU - Sparrow, David

AU - Regan, Elizabeth A

AU - Make, Barry J

AU - Hokanson, John E

AU - Murray, Tanda

AU - Hetmanski, Jacqueline B

AU - Pillai, Sreekumar G

AU - Kong, Xiangyang

AU - Anderson, Wayne H

AU - Tal-Singer, Ruth

AU - Lomas, David A

AU - Coxson, Harvey O

AU - Edwards, Lisa D

AU - MacNee, William

AU - Vestbo, Jørgen

AU - Yates, Julie C

AU - Agusti, Alvar

AU - Calverley, Peter M A

AU - Celli, Bartolome

AU - Crim, Courtney

AU - Rennard, Stephen

AU - Wouters, Emiel

AU - Bakke, Per

AU - Gulsvik, Amund

AU - Crapo, James D

AU - Beaty, Terri H

AU - Silverman, Edwin K

AU - ICGN Investigators

PY - 2012

Y1 - 2012

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 × 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 × 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.

UR - https://www.scopus.com/pages/publications/84856337050

U2 - 10.1093/hmg/ddr524

DO - 10.1093/hmg/ddr524

M3 - Journal article

C2 - 22080838

SN - 0964-6906

VL - 21

SP - 947

EP - 957

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 4

ER -

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

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