TY - JOUR
T1 - Effect of five genetic variants associated with lung function on the risk of chronic obstructive lung disease, and their joint effects on lung function
AU - Artigas, Maria Soler
AU - Wain, Louise V.
AU - Repapi, Emmanouela
AU - Obeidat, Ma'en
AU - Sayers, Ian
AU - Burton, Paul R.
AU - Johnson, Toby
AU - Zhao, Jing Hua
AU - Albrecht, Eva
AU - Dominiczak, Anna F.
AU - Kerr, Shona M.
AU - Smith, Blair H.
AU - Cadby, Gemma
AU - Hui, Jennie
AU - Palmer, Lyle J.
AU - Hingorani, Aroon D.
AU - Wannamethee, S. Goya
AU - Whincup, Peter H.
AU - Ebrahim, Shah
AU - Smith, George Davey
AU - Barroso, Ines
AU - Loos, Ruth J. F.
AU - Wareham, Nicholas J.
AU - Cooper, Cyrus
AU - Dennison, Elaine
AU - Shaheen, Seif O.
AU - Liu, Jason Z.
AU - Marchini, Jonathan
AU - Dahgam, Santosh
AU - Naluai, Asa Torinsson
AU - Olin, Anna-Carin
AU - Karrasch, Stefan
AU - Heinrich, Joachim
AU - Schulz, Holger
AU - McKeever, Tricia M.
AU - Pavord, Ian D.
AU - Heliovaara, Markku
AU - Ripatti, Samuli
AU - Surakka, Ida
AU - Blakey, John D.
AU - Kahonen, Mika
AU - Britton, John R.
AU - Nyberg, Fredrik
AU - Holloway, John W.
AU - Lawlor, Debbie A.
AU - Morris, Richard W.
AU - James, Alan L.
AU - Jackson, Cathy M.
AU - Hall, Ian P.
AU - Tobin, Martin D.
AU - SpiroMeta Consortium, Med Res Council Natl Survey Hlth D
PY - 2011/10/1
Y1 - 2011/10/1
N2 - 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 (beta = -72.21 ml, P = 3.90 x 10(-4)) and FEV1/FVC (beta = -1.53%, P = 6.3 x 10(-6)), and with COPD (odds ratio 1.63, P = 1.4 x 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.
AB - 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 (beta = -72.21 ml, P = 3.90 x 10(-4)) and FEV1/FVC (beta = -1.53%, P = 6.3 x 10(-6)), and with COPD (odds ratio 1.63, P = 1.4 x 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.
U2 - 10.1164/rccm.201102-0192OC
DO - 10.1164/rccm.201102-0192OC
M3 - Article
C2 - 21965014
SN - 1073-449X
VL - 184
SP - 786
EP - 795
JO - American Journal of Respiratory and Critical Care Medicine
JF - American Journal of Respiratory and Critical Care Medicine
IS - 7
ER -