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

Wellcome Trust Case Control Consortium; Emmanouela Repapi; Ian Sayers; Louise V Wain; Paul R Burton; Toby Johnson; Ma'en Obeidat; Jing Hua Zhao; Adaikalavan Ramasamy; Guangju Zhai; Veronique Vitart; Jennifer E Huffman; Wilmar Igl; Eva Albrecht; Panos Deloukas; John Henderson; Raquel Granell; Wendy L McArdle; Alicja R Rudnicka; Inês Barroso; Ruth J F Loos; Nicholas J Wareham; Linda Mustelin; Taina Rantanen; Ida Surakka; Medea Imboden; H Erich Wichmann; Ivica Grkovic; Stipan Jankovic; Lina Zgaga; Anna-Liisa Hartikainen; Leena Peltonen; Ulf Gyllensten; Asa Johansson; Ghazal Zaboli; Harry Campbell; Sarah H Wild; James F Wilson; Sven Gläser; Georg Homuth; Henry Völzke; Massimo Mangino; Nicole Soranzo; Tim D Spector; Ozren Polasek; Igor Rudan; Alan Wright; Andrew K MacLeod; Andrew Morris; David J Porteous; Caroline Hayward

doi:10.1038/ng.501

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

Wellcome Trust Case Control Consortium, Emmanouela Repapi, Ian Sayers, Louise V Wain, Paul R Burton, Toby Johnson, Ma'en Obeidat, Jing Hua Zhao, Adaikalavan Ramasamy, Guangju Zhai, Veronique Vitart, Jennifer E Huffman, Wilmar Igl, Eva Albrecht, Panos Deloukas, John Henderson, Raquel Granell, Wendy L McArdle, Alicja R Rudnicka, Inês BarrosoRuth J F Loos, Nicholas J Wareham, Linda Mustelin, Taina Rantanen, Ida Surakka, Medea Imboden, H Erich Wichmann, Ivica Grkovic, Stipan Jankovic, Lina Zgaga, Anna-Liisa Hartikainen, Leena Peltonen, Ulf Gyllensten, Asa Johansson, Ghazal Zaboli, Harry Campbell, Sarah H Wild, James F Wilson, Sven Gläser, Georg Homuth, Henry Völzke, Massimo Mangino, Nicole Soranzo, Tim D Spector, Ozren Polasek, Igor Rudan, Alan Wright, Andrew K MacLeod, Andrew Morris, David J Porteous, Caroline Hayward

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	36-44
Number of pages	9
Journal	Nature Genetics
Volume	42
Issue number	1
DOIs	https://doi.org/10.1038/ng.501
Publication status	Published - Jan 2010

Keywords / Materials (for Non-textual outputs)

Female
Forced Expiratory Volume
Gene Expression Profiling
Genome, Human
Genome-Wide Association Study
Glutathione Transferase
Humans
Lung
Male
Meta-Analysis as Topic
Microfilament Proteins
Polymorphism, Single Nucleotide
Pulmonary Disease, Chronic Obstructive
RNA, Messenger
Receptors, Immunologic
Receptors, Serotonin, 5-HT4
Respiratory Function Tests
Spirometry
Thrombospondins
Vital Capacity

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10.1038/ng.501

Genome-wide association study identifies five loci associated with lung function
Published in final edited form as: Nat Genet. Jan 2010; 42(1): 36–44.
Accepted author manuscript, 1.01 MB

http://www.nature.com/ng/journal/v42/n1/full/ng.501.html

Cite this

Wellcome Trust Case Control Consortium, 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., ... Hayward, C. (2010). Genome-wide association study identifies five loci associated with lung function. Nature Genetics, 42(1), 36-44. https://doi.org/10.1038/ng.501

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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 ",

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Wellcome Trust Case Control Consortium, Repapi, E, Sayers, I, Wain, LV, Burton, PR, Johnson, T, Obeidat, M, Zhao, JH, Ramasamy, A, Zhai, G, Vitart, V, Huffman, JE, Igl, W, Albrecht, E, Deloukas, P, Henderson, J, Granell, R, McArdle, WL, Rudnicka, AR, Barroso, I, Loos, RJF, Wareham, NJ, Mustelin, L, Rantanen, T, Surakka, I, Imboden, M, Wichmann, HE, Grkovic, I, Jankovic, S, Zgaga, L, Hartikainen, A-L, Peltonen, L, Gyllensten, U, Johansson, A, Zaboli, G, Campbell, H , Wild, SH , Wilson, JF, Gläser, S, Homuth, G, Völzke, H, Mangino, M, Soranzo, N, Spector, TD, Polasek, O, Rudan, I, Wright, A, MacLeod, AK, Morris, A, Porteous, DJ & Hayward, C 2010, 'Genome-wide association study identifies five loci associated with lung function', Nature Genetics, vol. 42, no. 1, pp. 36-44. https://doi.org/10.1038/ng.501

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KW - Meta-Analysis as Topic

KW - Microfilament Proteins

KW - Polymorphism, Single Nucleotide

KW - Pulmonary Disease, Chronic Obstructive

KW - RNA, Messenger

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JO - Nature Genetics

JF - Nature Genetics

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ER -

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

Abstract

Keywords / Materials (for Non-textual outputs)

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