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Genome-wide association study identifies five loci associated with lung function

Repapi, E. and Sayers, I. and Wain, L. V. and Burton, P. R. and Johnson, T. and Obeidat, M. and Zhao, J. H. and Ramasamy, A. and Zhai, G. and Vitart, V. and Huffman, J. E. and Igl, W. and Albrecht, E. and Deloukas, P. and Henderson, J. and Granell, R. and McArdle, W. L. and Rudnicka, A. R. and Barroso, I. and Loos, R. J. and Wareham, N. J. and Mustelin, L. and Rantanen, T. and Surakka, I. and Imboden, M. and Wichmann, H. E. and Grkovic, I. and Jankovic, S. and Zgaga, L. and Hartikainen, A. L. and Peltonen, L. and Gyllensten, U. and Johansson, A. and Zaboli, G. and Campbell, H. and Wild, S. H. and Wilson, J. F. and Glaser, S. and Homuth, G. and Volzke, H. and Mangino, M. and Soranzo, N. and Spector, T. D. and Polasek, O. and Rudan, I. and Wright, A. F. and Heliövaara, M. and Ripatti, S. and Pouta, A. and Naluai, A. T. and Olin, A. C. and Toren, K. and Cooper, M. N. and James, A. L. and Palmer, L. J. and Hingorani, A. D. and Wannamethee, S. G. and Whincup, P. H. and Smith, G. D. and Ebrahim, S. and McKeever, T. M. and Pavord, I. D. and MacLeod, A. K. and Morris, A. D. and Porteous, D. J. and Cooper, C. and Dennison, E. and Shaheen, S. and Karrasch, S. and Schnabel, E. and Schulz, H. and Grallert, H. and Bouatia-Naji N., and Delplanque, J. and Froguel, P. and Blakey, J. D. and Britton, J. R. and Morris, R. W. and Holloway, J. W. and Lawlor, D. A. and Hui, J. and Nyberg, F. and Jarvelin, M. R. and Jackson, C. and Kahonen, M. and Kaprio, J. and Probst-Hensch N. M., and Koch, B. and Hayward, C. and Evans, D. M. and Elliott, P. and Strachan, D. P. and Hall, I. P. and Tobin, M. D.. (2010) Genome-wide association study identifies five loci associated with lung function. Nature genetics, Vol. 42, H. 1. pp. 36-44.

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Official URL: http://edoc.unibas.ch/dok/A5842903

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Abstract

Pulmonary function measures are heritable traits that predict morbidity and mortality and define chronic obstructive pulmonary disease (COPD). We tested genome-wide association with forced expiratory volume in 1 s (FEV(1)) and the ratio of FEV(1) to forced vital capacity (FVC) in the SpiroMeta consortium (n = 20,288 individuals of European ancestry). We conducted a meta-analysis of top signals with data from direct genotyping (n > or = 32,184 additional individuals) and in silico summary association data from the CHARGE Consortium (n = 21,209) and the Health 2000 survey (n > or = 883). We confirmed the reported locus at 4q31 and identified associations with FEV(1) or FEV(1)/FVC and common variants at five additional loci: 2q35 in TNS1 (P = 1.11 x 10(-12)), 4q24 in GSTCD (2.18 x 10(-23)), 5q33 in HTR4 (P = 4.29 x 10(-9)), 6p21 in AGER (P = 3.07 x 10(-15)) and 15q23 in THSD4 (P = 7.24 x 10(-15)). mRNA analyses showed expression of TNS1, GSTCD, AGER, HTR4 and THSD4 in human lung tissue. These associations offer mechanistic insight into pulmonary function regulation and indicate potential targets for interventions to alleviate respiratory disease
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Chronic Disease Epidemiology > Genetic Epidemiology of Non-Communicable Diseases (Probst-Hensch)
03 Faculty of Medicine > Departement Public Health > Sozial- und Präventivmedizin > Genetic Epidemiology of Non-Communicable Diseases (Probst-Hensch)
UniBasel Contributors:Probst Hensch, Nicole
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Nature Publ.
ISSN:1061-4036
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:24 May 2013 09:22
Deposited On:24 May 2013 09:10

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