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Effect of 5 genetic variants associated with lung function on the risk of COPD, and their joint effects on lung function

Soler Artigas, María, Wain, Louise V., Repapi, Emmanouela, Obeidat, Ma'en, Sayers, Ian, Burton, Paul R., Johnson, Toby, Zhao, Jing Hua, Albrecht, Eva, Dominiczak, Anna F., Kerr, Shona M., Smith, Blair H., Cadby, Gemma, Hui, Jennie, Palmer, Lyle J., Hingorani, Aroon D., Wannamethee, S. Goya, Whincup, Peter H., Ebrahim, Shah, Smith, George Davey, Barroso, Inês, Loos, Ruth J.F., Wareham, Nicholas J., Cooper, Cyrus, Dennison, Elaine, Shaheen, Seif O., Liu, Jason Z., Marchini, Jonathan, Dahgam, Santosh, Naluai, Asa Torinsson, Olin, Anna-Carin, Karrasch, Stefan, Heinrich, Joachim, Schulz, Holger, McKeever, Tricia M, Pavord, Ian D, Heliövaara, Markku, Ripatti, Samuli, Surakka, Ida, Blakey, John D, Kähönen, Mika, Britton, John R, Nyberg, Fredrik, Holloway, John W, Lawlor, Debbie A, Morris, Richard W, James, Alan L, Jackson, Cathy M, Hall, Ian P, Tobin, Martin D and SpiroMeta Consortium, The NSHD Respiratory Study Team (2011) Effect of 5 genetic variants associated with lung function on the risk of COPD, and their joint effects on lung function American Journal of Respiratory and Critical Care Medicine (doi:10.1164/rccm.201102-0192OC). (PMID:21680943).

Record type: Article


Rationale: Genomic loci are associated with forced expiratory volume in one second (FEV1) or the ratio of FEV1 to forced vital capacity (FVC) in population samples, but their association with 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 evaluate joint effects on lung function and COPD of these SNPs, and variants at the previously reported locus near HHIP. Methods: Sampling from 12 population-based studies (n=31,422), we obtained genotype data on 3,284 COPD cases and 17,538 controls for sentinel SNPs in TNS1, GSTCD, HTR4, AGER and THSD4. In 24,648 individuals (including 2,890 COPD cases and 13,862 controls), 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.

Results: Association with COPD was significant for three loci (TNS1, GSTCD, 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=3.90x10-4) and FEV1/FVC (=-1.53%, P=6.35x10-6), and with COPD (OR=1.63, P=1.46x10-5).

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

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Published date: 16 June 2011
Keywords: forced expiratory volume in one second (fev1), forced vital capacity (fvc), genome-wide association study, modeling risk
Organisations: Clinical & Experimental Sciences


Local EPrints ID: 197201
ISSN: 1073-449X
PURE UUID: 15804d38-08dd-4da6-a427-28364c7d4a7e
ORCID for Cyrus Cooper: ORCID iD
ORCID for John W Holloway: ORCID iD

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Date deposited: 20 Sep 2011 10:35
Last modified: 18 Jul 2017 11:21

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Author: María Soler Artigas
Author: Louise V. Wain
Author: Emmanouela Repapi
Author: Ma'en Obeidat
Author: Ian Sayers
Author: Paul R. Burton
Author: Toby Johnson
Author: Jing Hua Zhao
Author: Eva Albrecht
Author: Anna F. Dominiczak
Author: Shona M. Kerr
Author: Blair H. Smith
Author: Gemma Cadby
Author: Jennie Hui
Author: Lyle J. Palmer
Author: Aroon D. Hingorani
Author: S. Goya Wannamethee
Author: Peter H. Whincup
Author: Shah Ebrahim
Author: George Davey Smith
Author: Inês Barroso
Author: Ruth J.F. Loos
Author: Nicholas J. Wareham
Author: Cyrus Cooper ORCID iD
Author: Elaine Dennison
Author: Seif O. Shaheen
Author: Jason Z. Liu
Author: Jonathan Marchini
Author: Santosh Dahgam
Author: Asa Torinsson Naluai
Author: Anna-Carin Olin
Author: Stefan Karrasch
Author: Joachim Heinrich
Author: Holger Schulz
Author: Tricia M McKeever
Author: Ian D Pavord
Author: Markku Heliövaara
Author: Samuli Ripatti
Author: Ida Surakka
Author: John D Blakey
Author: Mika Kähönen
Author: John R Britton
Author: Fredrik Nyberg
Author: John W Holloway ORCID iD
Author: Debbie A Lawlor
Author: Richard W Morris
Author: Alan L James
Author: Cathy M Jackson
Author: Ian P Hall
Author: Martin D Tobin
Author: The SpiroMeta Consortium

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