Effect of Five Genetic Variants Associated with Lung Function on the Risk of Chronic Obstructive Lung Disease, and Their Joint Effects on Lung Function
| العنوان: | Effect of Five Genetic Variants Associated with Lung Function on the Risk of Chronic Obstructive Lung Disease, and Their Joint Effects on Lung Function |
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| المؤلفون: | Blair H. Smith, Paul Burton, Jing Hua Zhao, Fredrik Nyberg, S Karrasch, Ruth J. F. Loos, Seif O. Shaheen, Tricia M. McKeever, A C Olin, Ma'en Obeidat, George Davey Smith, Åsa Torinsson Naluai, Markku Heliövaara, SG Wannamethee, Debbie A Lawlor, Mika Kähönen, Emmanouela Repapi, C.M. Jackson, Santosh Dahgam, E Albrecht, Ian Sayers, Ian D. Pavord, Jonathan Marchini, Ida Surakka, Holger Schulz, Nicholas J. Wareham, Martin D. Tobin, Ian P. Hall, Anna F. Dominiczak, Aroon D. Hingorani, Toby Johnson, Samuli Ripatti, Cyrus Cooper, Louise V. Wain, John D Blakey, Inês Barroso, Joachim Heinrich, Peter H. Whincup, Richard W Morris, S Ebrahim, John W. Holloway, Gemma Cadby, Lyle J. Palmer, Jennie Hui, Alan L. James, John Britton, Elaine M. Dennison, M. Soler Artigas, Shona M. Kerr, Jason Z. Liu |
| المصدر: | American Journal of Respiratory and Critical Care Medicine 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 F, Wareham, N J, Cooper, C, Dennison, E, Shaheen, S O, Liu, J Z, Marchini, J, Dahgam, S, Naluai, A T, Olin, A-C, Karrasch, S, Heinrich, J, Schulz, H, McKeever, T M, Pavord, I D, Heliövaara, M, Ripatti, S, Surakka, I, Blakey, J D, Kähönen, M, Britton, J R, Nyberg, F, Holloway, J W, Lawlor, D A, Morris, R W, James, A L, Jackson, C M, Hall, I P, Tobin, M D 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, vol. 184, no. 7, pp. 786-95 . https://doi.org/10.1164/rccm.201102-0192OCTest American Journal of Respiratory and Critical Care Medicine; Vol 184 Am. J. Respir. Crit. Care Med. 184, 786-795 (2011) |
| بيانات النشر: | American Thoracic Society, 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Male, Receptor for Advanced Glycation End Products, Vital Capacity, Genome-wide association study, Critical Care and Intensive Care Medicine, Gastroenterology, Thrombospondin 1, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Tensins, Forced Expiratory Volume, Receptors, Immunologic, Glutathione Transferase, 0303 health sciences, education.field_of_study, COPD, Framingham Risk Score, Microfilament Proteins, Articles, Middle Aged, respiratory system, Obstructive lung disease, 3. Good health, Europe, Female, circulatory and respiratory physiology, Adult, Pulmonary and Respiratory Medicine, FEV(1), FVC, genome-wide association study, modeling risk, medicine.medical_specialty, Population, Single-nucleotide polymorphism, Polymorphism, Single Nucleotide, 03 medical and health sciences, FEV1/FVC ratio, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, education, Aged, 030304 developmental biology, business.industry, Genetic Variation, Odds ratio, medicine.disease, respiratory tract diseases, 030228 respiratory system, Immunology, Receptors, Serotonin, 5-HT4, business, Genome-Wide Association Study |
| الوصف: | 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 (β = -72.21 ml, P = 3.90 × 10(-4)) and FEV1/FVC (β = -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. |
| وصف الملف: | application/pdf |
| تدمد: | 1535-4970 1073-449X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::77037dc26e60701042b70fd2360912a9Test https://doi.org/10.1164/rccm.201102-0192ocTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....77037dc26e60701042b70fd2360912a9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15354970 1073449X |
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