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

Genome-wide association study identifies five loci associated with lung function
Genome-wide association study identifies five loci associated with lung function
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 (FEV1) and the ratio of FEV1 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 ? 32,184 additional individuals) and in silico summary association data from the CHARGE Consortium (n = 21,209) and the Health 2000 survey (n ? 883). We confirmed the reported locus at 4q31 and identified associations with FEV1 or FEV1/FVC and common variants at five additional loci: 2q35 in TNS1 (P = 1.11 × 10?12), 4q24 in GSTCD (2.18 × 10?23), 5q33 in HTR4 (P = 4.29 × 10?9), 6p21 in AGER (P = 3.07 × 10?15) and 15q23 in THSD4 (P = 7.24 × 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
1061-4036
36-44
Repapi, E.
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Sayers, I.
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Wain, L.V.
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Burton, P.R.
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Johnson, T.
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Obeidat, M.
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Zhao, J.H.
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Ramasamy, A.
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Zhai, G.
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Vitart, V.
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Johansson, A.
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Zaboli, G.
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Glaser, S.
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Homuth, G.
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Volzke, H.
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Mangino, M.
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Soranzo, N.
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Spector, T.D.
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Polasek, O.
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Rudan, I.
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Wright, A.F.
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Heliovaara, M.
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Cooper, C.
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Dennison, E.
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Holloway, J.W.
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Wellcome Trust Case Control Consortium
Repapi, E.
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Sayers, I.
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Wain, L.V.
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Burton, P.R.
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Johnson, T.
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Obeidat, M.
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Zhao, J.H.
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Ramasamy, A.
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Zhai, G.
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Vitart, V.
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Huffman, J.E.
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Igl, W.
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Albrecht, E.
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Deloukas, P.
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Henderson, J.
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Granell, R.
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McArdle, W.L.
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Rudnicka, A.R.
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Barroso, I.
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Loos, R.J.F.
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Wareham, N.J.
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Mustelin, L.
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Rantanen, T.
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Surakka, I.
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Imboden, M.
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Wichmann, H.E.
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Grkovic, I.
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Jankovic, S.
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Zgaga, L.
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Hartikainen, A.L.
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Peltonen, L.
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Gyllensten, U.
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Johansson, A.
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Zaboli, G.
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Campbell, H.
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Wild, S.H.
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Wilson, J.F.
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Glaser, S.
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Homuth, G.
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Volzke, H.
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Mangino, M.
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Soranzo, N.
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Spector, T.D.
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Polasek, O.
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Rudan, I.
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Wright, A.F.
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Heliovaara, M.
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Cooper, C.
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Dennison, E.
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Holloway, J.W.
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Repapi, E., Sayers, I., Wain, L.V., Burton, P.R., Johnson, T., Obeidat, M., Zhao, J.H., Ramasamy, A., Zhai, G., Vitart, V., Huffman, J.E., Igl, W., Albrecht, E., Deloukas, P., Henderson, J., Granell, R., McArdle, W.L., Rudnicka, A.R., Barroso, I., Loos, R.J.F., Wareham, N.J., Mustelin, L., Rantanen, T., Surakka, I., Imboden, M., Wichmann, H.E., Grkovic, I., Jankovic, S., Zgaga, L., Hartikainen, A.L., Peltonen, L., Gyllensten, U., Johansson, A., Zaboli, G., Campbell, H., Wild, S.H., Wilson, J.F., Glaser, S., Homuth, G., Volzke, H., Mangino, M., Soranzo, N., Spector, T.D., Polasek, O., Rudan, I., Wright, A.F., Heliovaara, M., Cooper, C., Dennison, E. and Holloway, J.W. , Wellcome Trust Case Control Consortium (2010) Genome-wide association study identifies five loci associated with lung function. Nature Genetics, 42 (1), 36-44. (doi:10.1038/ng.501).

Record type: Article

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 (FEV1) and the ratio of FEV1 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 ? 32,184 additional individuals) and in silico summary association data from the CHARGE Consortium (n = 21,209) and the Health 2000 survey (n ? 883). We confirmed the reported locus at 4q31 and identified associations with FEV1 or FEV1/FVC and common variants at five additional loci: 2q35 in TNS1 (P = 1.11 × 10?12), 4q24 in GSTCD (2.18 × 10?23), 5q33 in HTR4 (P = 4.29 × 10?9), 6p21 in AGER (P = 3.07 × 10?15) and 15q23 in THSD4 (P = 7.24 × 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

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More information

Published date: January 2010
Organisations: Human Genetics, Infection Inflammation & Immunity

Identifiers

Local EPrints ID: 72185
URI: http://eprints.soton.ac.uk/id/eprint/72185
ISSN: 1061-4036
PURE UUID: 3e94ab62-a635-490f-8a15-bc8c29b970a7
ORCID for C. Cooper: ORCID iD orcid.org/0000-0003-3510-0709
ORCID for E. Dennison: ORCID iD orcid.org/0000-0002-3048-4961
ORCID for J.W. Holloway: ORCID iD orcid.org/0000-0001-9998-0464

Catalogue record

Date deposited: 28 Jan 2010
Last modified: 18 Mar 2024 02:47

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Contributors

Author: E. Repapi
Author: I. Sayers
Author: L.V. Wain
Author: P.R. Burton
Author: T. Johnson
Author: M. Obeidat
Author: J.H. Zhao
Author: A. Ramasamy
Author: G. Zhai
Author: V. Vitart
Author: J.E. Huffman
Author: W. Igl
Author: E. Albrecht
Author: P. Deloukas
Author: J. Henderson
Author: R. Granell
Author: W.L. McArdle
Author: A.R. Rudnicka
Author: I. Barroso
Author: R.J.F. Loos
Author: N.J. Wareham
Author: L. Mustelin
Author: T. Rantanen
Author: I. Surakka
Author: M. Imboden
Author: H.E. Wichmann
Author: I. Grkovic
Author: S. Jankovic
Author: L. Zgaga
Author: A.L. Hartikainen
Author: L. Peltonen
Author: U. Gyllensten
Author: A. Johansson
Author: G. Zaboli
Author: H. Campbell
Author: S.H. Wild
Author: J.F. Wilson
Author: S. Glaser
Author: G. Homuth
Author: H. Volzke
Author: M. Mangino
Author: N. Soranzo
Author: T.D. Spector
Author: O. Polasek
Author: I. Rudan
Author: A.F. Wright
Author: M. Heliovaara
Author: C. Cooper ORCID iD
Author: E. Dennison ORCID iD
Author: J.W. Holloway ORCID iD
Corporate Author: Wellcome Trust Case Control Consortium

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