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

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; Ines 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 Glaeser; Georg Homuth; Henry Voelzke; Massimo Mangino; Nicole Soranzo; Tim D. Spector; Ozren Polasek; Igor Rudan; Alan F. Wright; Markku Heliovaara; Samuli Ripatti; Anneli Pouta; Andrew D. Morris; Wellcome Trust Case Control Consor, NSHD Resp Study Team

doi:10.1038/ng.501

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

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, Ines Barroso, Ruth J. F. LoosNicholas 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 Glaeser, Georg Homuth, Henry Voelzke, Massimo Mangino, Nicole Soranzo, Tim D. Spector, Ozren Polasek, Igor Rudan, Alan F. Wright, Markku Heliovaara, Samuli Ripatti, Anneli Pouta, Andrew D. Morris, Wellcome Trust Case Control Consor, NSHD Resp Study Team

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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 (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 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-U51
Number of pages	10
Journal	Nature Genetics
Volume	42
Issue number	1
DOIs	https://doi.org/10.1038/ng.501
Publication status	Published - Jan 2010

Keywords

ADVANCED GLYCATION ENDPRODUCTS
IDIOPATHIC PULMONARY-FIBROSIS
IN-VITRO
RECEPTOR
HEIGHT
HEALTH
POPULATION
MORTALITY
VARIANTS
CANCER

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/ng.501

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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., ... Wellcome Trust Case Control Consor, NSHD Resp Study Team (2010). Genome-wide association study identifies five loci associated with lung function. Nature Genetics, 42(1), 36-U51. https://doi.org/10.1038/ng.501

@article{69a882dd33904c8689715d422f0dde04,

title = "Genome-wide association study identifies five loci associated with lung function",

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 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.",

keywords = "ADVANCED GLYCATION ENDPRODUCTS, IDIOPATHIC PULMONARY-FIBROSIS, IN-VITRO, RECEPTOR, HEIGHT, HEALTH, POPULATION, MORTALITY, VARIANTS, CANCER",

author = "Emmanouela Repapi and Ian Sayers and Wain, {Louise V.} and Burton, {Paul R.} and Toby Johnson and Ma'en Obeidat and Zhao, {Jing Hua} and Adaikalavan Ramasamy and Guangju Zhai and Veronique Vitart and Huffman, {Jennifer E.} and Wilmar Igl and Eva Albrecht and Panos Deloukas and John Henderson and Raquel Granell and McArdle, {Wendy L.} and Rudnicka, {Alicja R.} and Ines Barroso and Loos, {Ruth J. F.} and Wareham, {Nicholas J.} and Linda Mustelin and Taina Rantanen and Ida Surakka and Medea Imboden and Wichmann, {H. Erich} and Ivica Grkovic and Stipan Jankovic and Lina Zgaga and Anna-Liisa Hartikainen and Leena Peltonen and Ulf Gyllensten and Asa Johansson and Ghazal Zaboli and Harry Campbell and Wild, {Sarah H.} and Wilson, {James F.} and Sven Glaeser and Georg Homuth and Henry Voelzke and Massimo Mangino and Nicole Soranzo and Spector, {Tim D.} and Ozren Polasek and Igor Rudan and Wright, {Alan F.} and Markku Heliovaara and Samuli Ripatti and Anneli Pouta and Morris, {Andrew D.} and {Wellcome Trust Case Control Consor, NSHD Resp Study Team}",

year = "2010",

month = jan,

doi = "10.1038/ng.501",

language = "English",

volume = "42",

pages = "36--U51",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "1",

}

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, Glaeser, S, Homuth, G, Voelzke, H, Mangino, M, Soranzo, N, Spector, TD, Polasek, O, Rudan, I, Wright, AF, Heliovaara, M, Ripatti, S, Pouta, A, Morris, AD & Wellcome Trust Case Control Consor, NSHD Resp Study Team 2010, 'Genome-wide association study identifies five loci associated with lung function', Nature Genetics, vol. 42, no. 1, pp. 36-U51. https://doi.org/10.1038/ng.501

TY - JOUR

T1 - Genome-wide association study identifies five loci associated with lung function

AU - Repapi, Emmanouela

AU - Sayers, Ian

AU - Wain, Louise V.

AU - Burton, Paul R.

AU - Johnson, Toby

AU - Obeidat, Ma'en

AU - Zhao, Jing Hua

AU - Ramasamy, Adaikalavan

AU - Zhai, Guangju

AU - Vitart, Veronique

AU - Huffman, Jennifer E.

AU - Igl, Wilmar

AU - Albrecht, Eva

AU - Deloukas, Panos

AU - Henderson, John

AU - Granell, Raquel

AU - McArdle, Wendy L.

AU - Rudnicka, Alicja R.

AU - Barroso, Ines

AU - Loos, Ruth J. F.

AU - Wareham, Nicholas J.

AU - Mustelin, Linda

AU - Rantanen, Taina

AU - Surakka, Ida

AU - Imboden, Medea

AU - Wichmann, H. Erich

AU - Grkovic, Ivica

AU - Jankovic, Stipan

AU - Zgaga, Lina

AU - Hartikainen, Anna-Liisa

AU - Peltonen, Leena

AU - Gyllensten, Ulf

AU - Johansson, Asa

AU - Zaboli, Ghazal

AU - Campbell, Harry

AU - Wild, Sarah H.

AU - Wilson, James F.

AU - Glaeser, Sven

AU - Homuth, Georg

AU - Voelzke, Henry

AU - Mangino, Massimo

AU - Soranzo, Nicole

AU - Spector, Tim D.

AU - Polasek, Ozren

AU - Rudan, Igor

AU - Wright, Alan F.

AU - Heliovaara, Markku

AU - Ripatti, Samuli

AU - Pouta, Anneli

AU - Morris, Andrew D.

AU - Wellcome Trust Case Control Consor, NSHD Resp Study Team

PY - 2010/1

Y1 - 2010/1

N2 - 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 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.

AB - 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 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.

KW - ADVANCED GLYCATION ENDPRODUCTS

KW - IDIOPATHIC PULMONARY-FIBROSIS

KW - IN-VITRO

KW - RECEPTOR

KW - HEIGHT

KW - HEALTH

KW - POPULATION

KW - MORTALITY

KW - VARIANTS

KW - CANCER

U2 - 10.1038/ng.501

DO - 10.1038/ng.501

M3 - Article

C2 - 20010834

SN - 1061-4036

VL - 42

SP - 36-U51

JO - Nature Genetics

JF - Nature Genetics

IS - 1

ER -

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

Abstract

Keywords

UN SDGs

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