Effect of five genetic variants associated with lung function on the risk of chronic obstructive lung disease, and their joint effects on lung function

Soler Artigas, M. et al. (2011) Effect of five genetic variants associated with lung function on the risk of chronic obstructive lung 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)

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Publisher's URL: http://dx.doi.org/10.1164/rccm.201102-0192OC


<i>Rationale:</i> Genomic loci are associated with FEV(1) or the ratio of FEV(1) 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.<p></p> <i>Objectives:</i> 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. <p></p> <i>Methods:</i> 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. <p></p> <i>Measurements and Main Results:</i> 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 FEV(1) (β= -72.21 ml, P = 3.90 x 10<sup>-4</sup>) and FEV<sub>1</sub>/FVC (β= -1.53%, P = 6.3 x 10<sup>-6</sup>), and with COPD (odds ratio 1.63, P = 1.4 x 10<sup>-5</sup>).<p></p> <i>Conclusions:</i> 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. <p></p>

Item Type:Articles
Glasgow Author(s) Enlighten ID:Dominiczak, Professor Anna
Authors: Soler Artigas, M., Wain, L. V., Repapi, E., Obeidat, M.'e., 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.F., Wareham, N. J., Cooper, C., Dennison, E., Shaheen, S. O., Liu, J. Z., Marchini, J., Dahgam, S., Naluai, Å. 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.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:American Journal of Respiratory and Critical Care Medicine
Publisher:American Thoracic Society
ISSN (Online):1535-4970

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