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Effect of five genetic variants associated with lung function on the risk of Chronic Obstructive Disease, and their joint effects on lung function

Soler Artigas, M., Wain, L.V., Repapi, E., Obeidat, M., Sayers, I., Burton, P.R., Johnson, T., Zhao, J.H., Albrecht, E., Dominiczak, A.F., Kerr, S.M., Smith, B.H., Cadby, G., Hui, J., Palmer, L.J., Hingorani, A.D., Wannamethee, S.G., Whincup, P.H., Ebrahim, S., Smith, G.D., Barroso, I., Loos, R.J., Wareham, N.J., Cooper, C., Dennison, E., Shaheen, S.O., Lui, J.Z., Marchini, J., Dahgam, S., Naluai, A.T., Olin, A.C., Karrasch, S., Heinrich, J., Schulz, H., McKeever, T.M., Pavord, I.D., Heliovaara, M., Ripatti, S., Surakka, I., Blakey, J.D., Kahonen, M., Britton, J.R., Nyberg, F., Holloway, J.W., Lawlor, D.A., Morris, R.W., James, A.L., Jackson, C.M., Hall, I.P. and Tobin, M.D. Medical Research Council National Survey of Health and Development (NSHD) Respiratory Study Team (2011) Effect of five genetic variants associated with lung function on the risk of Chronic Obstructive Disease, and their joint effects on lung function American Journal of Respiratory and Critical Care Medicine, 184, (7), pp. 786-795. (doi:10.1164/rccm.201102-0192OC). (PMID:21965014).

Record type: Article


Rationale: Genomic loci are associated with FEV1 or the ratio of FEV1 to FVC in population samples, but their association with chronic obstructive pulmonary disease (COPD) has not yet been proven, nor have their combined effects on lung function and COPD been studied.

Objectives: To test association with COPD of variants at five loci (TNS1, GSTCD, HTR4, AGER, and THSD4) and to evaluate joint effects on lung function and COPD of these single-nucleotide polymorphisms (SNPs), and variants at the previously reported locus near HHIP.

Methods: By sampling from 12 population-based studies (n = 31,422), we obtained genotype data on 3,284 COPD case subjects and 17,538 control subjects for sentinel SNPs in TNS1, GSTCD, HTR4, AGER, and THSD4. In 24,648 individuals (including 2,890 COPD case subjects and 13,862 control subjects), we additionally obtained genotypes for rs12504628 near HHIP. Each allele associated with lung function decline at these six SNPs contributed to a risk score. We studied the association of the risk score to lung function and COPD.

Measurements and Main Results: Association with COPD was significant for three loci (TNS1, GSTCD, and HTR4) and the previously reported HHIP locus, and suggestive and directionally consistent for AGER and TSHD4. Compared with the baseline group (7 risk alleles), carrying 10–12 risk alleles was associated with a reduction in FEV1 (? = –72.21 ml, P = 3.90 × 10?4) and FEV1/FVC (? = –1.53%, P = 6.35 × 10?6), and with COPD (odds ratio = 1.63, P = 1.46 × 10?5).

Conclusions: Variants in TNS1, GSTCD, and HTR4 are associated with COPD. Our highest risk score category was associated with a 1.6-fold higher COPD risk than the population average score.

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e-pub ahead of print date: 16 June 2011
Published date: 1 October 2011
Organisations: Faculty of Medicine


Local EPrints ID: 206339
ISSN: 1073-449X
PURE UUID: 090c8d5a-e44e-4807-91a7-94ba24c170f9
ORCID for C. Cooper: ORCID iD

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Date deposited: 19 Dec 2011 17:12
Last modified: 18 Jul 2017 11:02

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Author: M. Soler Artigas
Author: L.V. Wain
Author: E. Repapi
Author: M. Obeidat
Author: I. Sayers
Author: P.R. Burton
Author: T. Johnson
Author: J.H. Zhao
Author: E. Albrecht
Author: A.F. Dominiczak
Author: S.M. Kerr
Author: B.H. Smith
Author: G. Cadby
Author: J. Hui
Author: L.J. Palmer
Author: A.D. Hingorani
Author: S.G. Wannamethee
Author: P.H. Whincup
Author: S. Ebrahim
Author: G.D. Smith
Author: I. Barroso
Author: R.J. Loos
Author: N.J. Wareham
Author: C. Cooper ORCID iD
Author: E. Dennison
Author: S.O. Shaheen
Author: J.Z. Lui
Author: J. Marchini
Author: S. Dahgam
Author: A.T. Naluai
Author: A.C. Olin
Author: S. Karrasch
Author: J. Heinrich
Author: H. Schulz
Author: T.M. McKeever
Author: I.D. Pavord
Author: M. Heliovaara
Author: S. Ripatti
Author: I. Surakka
Author: J.D. Blakey
Author: M. Kahonen
Author: J.R. Britton
Author: F. Nyberg
Author: J.W. Holloway
Author: D.A. Lawlor
Author: R.W. Morris
Author: A.L. James
Author: C.M. Jackson
Author: I.P. Hall
Author: M.D. Tobin

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