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

被引：180

作者：

Cho, Michael H. ^{[1
,2
]}

Castaldi, Peter J. ^{[1
]}

Wan, Emily S. ^{[1
,2
]}

Siedlinski, Mateusz ^{[1
]}

Hersh, Craig P. ^{[1
,2
]}

Demeo, Dawn L. ^{[1
,2
]}

Himes, Blanca E. ^{[1
]}

Sylvia, Jody S. ^{[1
]}

Klanderman, Barbara J. ^{[1
]}

Ziniti, John P. ^{[1
]}

Lange, Christoph ^{[3
]}

Litonjua, Augusto A. ^{[1
,2
]}

Sparrow, David ^{[4
,5
,6
]}

Regan, Elizabeth A. ^{[7
]}

Make, Barry J. ^{[7
]}

Hokanson, John E. ^{[8
]}

Murray, Tanda ^{[9
]}

Hetmanski, Jacqueline B. ^{[9
]}

Pillai, Sreekumar G. ^{[10
]}

Kong, Xiangyang

Anderson, Wayne H. ^{[10
]}

Tal-Singer, Ruth

Lomas, David A. ^{[11
]}

Coxson, Harvey O. ^{[12
,13
]}

Edwards, Lisa D. ^{[10
]}

MacNee, William ^{[14
]}

Vestbo, Jorgen ^{[15
]}

Yates, Julie C. ^{[10
]}

Agusti, Alvar ^{[16
,17
]}

Calverley, Peter M. A. ^{[18
]}

Celli, Bartolome ^{[2
]}

Crim, Courtney ^{[10
]}

Rennard, Stephen ^{[19
]}

Wouters, Emiel ^{[20
]}

Bakke, Per ^{[21
,22
]}

Gulsvik, Amund ^{[21
,22
]}

Crapo, James D. ^{[7
]}

Beaty, Terri H. ^{[9
]}

Silverman, Edwin K. ^{[1
,2
]}

机构：

[1] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA

[2] Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA

[3] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA

[4] Boston Univ, Sch Publ Hlth, Boston, MA USA

[5] Boston Univ, Sch Med, Boston, MA 02118 USA

[6] Vet Adm Boston Healthcare Syst, Boston, MA USA

[7] Natl Jewish Hlth, Denver, CO USA

[8] Univ Colorado Denver, Colorado Sch Publ Hlth, Dept Epidemiol, Aurora, CO USA

[9] Johns Hopkins Sch Publ Hlth, Baltimore, MD USA

[10] GlaxoSmithKline Res & Dev Ltd, Res Triangle Pk, NC USA

[11] Univ Cambridge, Cambridge Inst Med Res, Cambridge, England

[12] Univ British Columbia, Dept Radiol, Vancouver, BC, Canada

[13] James Hogg Res Ctr, Inst Heart & Lung Hlth, Vancouver, BC, Canada

[14] Univ Edinburgh, Edinburgh, Midlothian, Scotland

[15] Univ Copenhagen, Hvidovre Hosp, DK-2650 Hvidovre, Denmark

[16] Univ Pompeu Fabra Barcelona, Hosp Clin IDIBAPS, Thorax Inst, Mallorca, Spain

[17] Fdn Caubet Cimera, CIBER Enfermedades Resp CIBERES, Mallorca, Spain

[18] Aintree Univ Hosp NHS Fdn Trust, Liverpool L9 7AL, Merseyside, England

[19] Univ Nebraska, Omaha, NE 68182 USA

[20] Univ Maastricht, Maastricht, Netherlands

[21] Haukeland Hosp, N-5021 Bergen, Norway

[22] Univ Bergen, Inst Med, Bergen, Norway

来源：

HUMAN MOLECULAR GENETICS | 2012年 / 21卷 / 04期

基金：

美国医疗保健研究与质量局; 美国国家卫生研究院;

关键词：

OBSTRUCTIVE PULMONARY-DISEASE; AIR-FLOW OBSTRUCTION; SMOKING-CESSATION INTERVENTION; LUNG-CANCER; GENETIC EPIDEMIOLOGY; NICOTINE METABOLISM; LINKAGE ANALYSIS; CYP2A6; ALLELES; FOLLOW-UP; RISK;

D O I：

10.1093/hmg/ddr524

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 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 FEV1 (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.

引用

页码：947 / 957

页数：11

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