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 journalArticle

160 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 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.

Original languageEnglish (US)
Article numberddr524
Pages (from-to)947-957
Number of pages11
JournalHuman Molecular Genetics
Volume21
Issue number4
DOIs
StatePublished - Feb 1 2012

Fingerprint

Genome-Wide Association Study
Chronic Obstructive Pulmonary Disease
Chromosomes
Bronchodilator Agents
Linkage Disequilibrium
Emphysema
Norway
Meta-Analysis
Biomarkers
Smoking
Genome

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Cho, M. H., Castaldi, P. J., Wan, E. S., Siedlinski, M., Hersh, C. P., Demeo, D. L., ... 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. [ddr524]. https://doi.org/10.1093/hmg/ddr524

A genome-wide association study of COPD identifies a susceptibility locus on chromosome 19q13. / Cho, Michael H.; Castaldi, Peter J.; Wan, Emily S.; Siedlinski, Mateusz; Hersh, Craig P.; Demeo, Dawn L.; Himes, Blanca E.; Sylvia, Jody S.; Klanderman, Barbara J.; Ziniti, John P.; Lange, Christoph; Litonjua, Augusto A.; Sparrow, David; Regan, Elizabeth A.; Make, Barry J.; Hokanson, John E.; Murray, Tanda; Hetmanski, Jacqueline B.; Pillai, Sreekumar G.; Kong, Xiangyang; Anderson, Wayne H.; Tal-Singer, Ruth; Lomas, David A.; Coxson, Harvey O.; Edwards, Lisa D.; MacNee, William; Vestbo, Jørgen; Yates, Julie C.; Agusti, Alvar; Calverley, Peter M.A.; Celli, Bartolome; Crim, Courtney; Rennard, Stephen; Wouters, Emiel; Bakke, Per; Gulsvik, Amund; Crapo, James D.; Beaty, Terri H.; Silverman, Edwin K.

In: Human Molecular Genetics, Vol. 21, No. 4, ddr524, 01.02.2012, p. 947-957.

Research output: Contribution to journalArticle

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 2012, 'A genome-wide association study of COPD identifies a susceptibility locus on chromosome 19q13', Human Molecular Genetics, vol. 21, no. 4, ddr524, pp. 947-957. https://doi.org/10.1093/hmg/ddr524
Cho MH, Castaldi PJ, Wan ES, Siedlinski M, Hersh CP, Demeo DL et al. A genome-wide association study of COPD identifies a susceptibility locus on chromosome 19q13. Human Molecular Genetics. 2012 Feb 1;21(4):947-957. ddr524. https://doi.org/10.1093/hmg/ddr524
Cho, Michael H. ; Castaldi, Peter J. ; Wan, Emily S. ; Siedlinski, Mateusz ; Hersh, Craig P. ; Demeo, Dawn L. ; Himes, Blanca E. ; Sylvia, Jody S. ; Klanderman, Barbara J. ; Ziniti, John P. ; Lange, Christoph ; Litonjua, Augusto A. ; Sparrow, David ; Regan, Elizabeth A. ; Make, Barry J. ; Hokanson, John E. ; Murray, Tanda ; Hetmanski, Jacqueline B. ; Pillai, Sreekumar G. ; Kong, Xiangyang ; Anderson, Wayne H. ; Tal-Singer, Ruth ; Lomas, David A. ; Coxson, Harvey O. ; Edwards, Lisa D. ; MacNee, William ; Vestbo, Jørgen ; Yates, Julie C. ; Agusti, Alvar ; Calverley, Peter M.A. ; Celli, Bartolome ; Crim, Courtney ; Rennard, Stephen ; Wouters, Emiel ; Bakke, Per ; Gulsvik, Amund ; Crapo, James D. ; Beaty, Terri H. ; Silverman, Edwin K. / A genome-wide association study of COPD identifies a susceptibility locus on chromosome 19q13. In: Human Molecular Genetics. 2012 ; Vol. 21, No. 4. pp. 947-957.
@article{3dceb1765d704ab6a475094d53a49bf9,
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 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.",
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.}",
year = "2012",
month = "2",
day = "1",
doi = "10.1093/hmg/ddr524",
language = "English (US)",
volume = "21",
pages = "947--957",
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.

PY - 2012/2/1

Y1 - 2012/2/1

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 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.

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 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.

UR - http://www.scopus.com/inward/record.url?scp=84856337050&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84856337050&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddr524

DO - 10.1093/hmg/ddr524

M3 - Article

C2 - 22080838

AN - SCOPUS:84856337050

VL - 21

SP - 947

EP - 957

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 4

M1 - ddr524

ER -