A Comprehensive Evaluation of Potential Lung Function Associated Genes in the SpiroMeta General Population Sample

Ma'en Obeidat; Louise V. Wain; Nick Shrine; Noor Kalsheker; Maria Soler Artigas; Emmanouela Repapi; Paul R. Burton; Toby Johnson; Adaikalavan Ramasamy; Jing Hua Zhao; Guangju Zhai; Jennifer E. Huffman; Veronique Vitart; Eva Albrecht; Wilmar Igl; Anna-Liisa Hartikainen; Anneli Pouta; Gemma Cadby; Jennie Hui; Lyle J. Palmer; David Hadley; Wendy L. McArdle; Alicja R. Rudnicka; Ines Barroso; Ruth J. F. Loos; Nicholas J. Wareham; Massimo Mangino; Nicole Soranzo; Tim D. Spector; Sven Glaeser; Georg Homuth; Henry Voelzke; Panos Deloukas; Raquel Granell; John Henderson; Ivica Grkovic; Stipan Jankovic; Lina Zgaga; Ozren Polasek; Igor Rudan; Alan F. Wright; Harry Campbell; Sarah H. Wild; James F. Wilson; Joachim Heinrich; Medea Imboden; Nicole M. Probst-Hensch; Ulf Gyllensten; Asa Johansson; Ghazal Zaboli; Linda Mustelin; Taina Rantanen; Ida Surakka; Jaakko Kaprio; Marjo-Riitta Jarvelin; Caroline Hayward; David M. Evans; Beate Koch; Arthur William Musk; Paul Elliott; David P. Strachan; Martin D. Tobin; Ian Sayers; Ian P. Hall

doi:10.1371/journal.pone.0019382

A Comprehensive Evaluation of Potential Lung Function Associated Genes in the SpiroMeta General Population Sample

Ma'en Obeidat, Louise V. Wain, Nick Shrine, Noor Kalsheker, Maria Soler Artigas, Emmanouela Repapi, Paul R. Burton, Toby Johnson, Adaikalavan Ramasamy, Jing Hua Zhao, Guangju Zhai, Jennifer E. Huffman, Veronique Vitart, Eva Albrecht, Wilmar Igl, Anna-Liisa Hartikainen, Anneli Pouta, Gemma Cadby, Jennie Hui, Lyle J. PalmerDavid Hadley, Wendy L. McArdle, Alicja R. Rudnicka, Ines Barroso, Ruth J. F. Loos, Nicholas J. Wareham, Massimo Mangino, Nicole Soranzo, Tim D. Spector, Sven Glaeser, Georg Homuth, Henry Voelzke, Panos Deloukas, Raquel Granell, John Henderson, Ivica Grkovic, Stipan Jankovic, Lina Zgaga, Ozren Polasek, Igor Rudan, Alan F. Wright, Harry Campbell, Sarah H. Wild, James F. Wilson, Joachim Heinrich, Medea Imboden, Nicole M. Probst-Hensch, Ulf Gyllensten, Asa Johansson, Ghazal Zaboli, Linda Mustelin, Taina Rantanen, Ida Surakka, Jaakko Kaprio, Marjo-Riitta Jarvelin, Caroline Hayward, David M. Evans, Beate Koch, Arthur William Musk, Paul Elliott, David P. Strachan, Martin D. Tobin, Ian Sayers, Ian P. Hall

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Abstract

Rationale: Lung function measures are heritable traits that predict population morbidity and mortality and are essential for the diagnosis of chronic obstructive pulmonary disease (COPD). Variations in many genes have been reported to affect these traits, but attempts at replication have provided conflicting results. Recently, we undertook a meta-analysis of Genome Wide Association Study (GWAS) results for lung function measures in 20,288 individuals from the general population (the SpiroMeta consortium). Objectives: To comprehensively analyse previously reported genetic associations with lung function measures, and to investigate whether single nucleotide polymorphisms (SNPs) in these genomic regions are associated with lung function in a large population sample. Methods: We analysed association for SNPs tagging 130 genes and 48 intergenic regions (+/-10 kb), after conducting a systematic review of the literature in the PubMed database for genetic association studies reporting lung function associations. Results: The analysis included 16,936 genotyped and imputed SNPs. No loci showed overall significant association for FEV1 or FEV1/FVC traits using a carefully defined significance threshold of 1.3 x 10(-5). The most significant loci associated with FEV1 include SNPs tagging MACROD2 (P = 6.81 x 10(-5)), CNTN5 (P = 4.37 x 10(-4)), and TRPV4 (P = 1.58 x 10(-3)). Among ever-smokers, SERPINA1 showed the most significant association with FEV1 (P = 8.41 x 10(-5)), followed by PDE4D (P = 1.22 x 10(-4)). The strongest association with FEV1/FVC ratio was observed with ABCC1 (P = 4.38 x 10(-4)), and ESR1 (P = 5.42 x 10(-4)) among ever-smokers. Conclusions: Polymorphisms spanning previously associated lung function genes did not show strong evidence for association with lung function measures in the SpiroMeta consortium population. Common SERPINA1 polymorphisms may affect FEV1 among smokers in the general population.

Original language	English
Article number	e19382
Journal	PL o S One
Volume	6
Issue number	5
DOIs	https://doi.org/10.1371/journal.pone.0019382
Publication status	Published - 2011

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Obeidat, M., Wain, L. V., Shrine, N., Kalsheker, N., Artigas, M. S., Repapi, E., Burton, P. R., Johnson, T., Ramasamy, A., Zhao, J. H., Zhai, G., Huffman, J. E., Vitart, V., Albrecht, E., Igl, W., Hartikainen, A.-L., Pouta, A., Cadby, G., Hui, J., ... Hall, I. P. (2011). A Comprehensive Evaluation of Potential Lung Function Associated Genes in the SpiroMeta General Population Sample. PL o S One , 6(5), Article e19382. https://doi.org/10.1371/journal.pone.0019382

@article{f1d18141e45e4082aa249c021b9e38cd,

title = "A Comprehensive Evaluation of Potential Lung Function Associated Genes in the SpiroMeta General Population Sample",

abstract = "Rationale: Lung function measures are heritable traits that predict population morbidity and mortality and are essential for the diagnosis of chronic obstructive pulmonary disease (COPD). Variations in many genes have been reported to affect these traits, but attempts at replication have provided conflicting results. Recently, we undertook a meta-analysis of Genome Wide Association Study (GWAS) results for lung function measures in 20,288 individuals from the general population (the SpiroMeta consortium). Objectives: To comprehensively analyse previously reported genetic associations with lung function measures, and to investigate whether single nucleotide polymorphisms (SNPs) in these genomic regions are associated with lung function in a large population sample. Methods: We analysed association for SNPs tagging 130 genes and 48 intergenic regions (+/-10 kb), after conducting a systematic review of the literature in the PubMed database for genetic association studies reporting lung function associations. Results: The analysis included 16,936 genotyped and imputed SNPs. No loci showed overall significant association for FEV1 or FEV1/FVC traits using a carefully defined significance threshold of 1.3 x 10(-5). The most significant loci associated with FEV1 include SNPs tagging MACROD2 (P = 6.81 x 10(-5)), CNTN5 (P = 4.37 x 10(-4)), and TRPV4 (P = 1.58 x 10(-3)). Among ever-smokers, SERPINA1 showed the most significant association with FEV1 (P = 8.41 x 10(-5)), followed by PDE4D (P = 1.22 x 10(-4)). The strongest association with FEV1/FVC ratio was observed with ABCC1 (P = 4.38 x 10(-4)), and ESR1 (P = 5.42 x 10(-4)) among ever-smokers. Conclusions: Polymorphisms spanning previously associated lung function genes did not show strong evidence for association with lung function measures in the SpiroMeta consortium population. Common SERPINA1 polymorphisms may affect FEV1 among smokers in the general population.",

author = "Ma'en Obeidat and Wain, {Louise V.} and Nick Shrine and Noor Kalsheker and Artigas, {Maria Soler} and Emmanouela Repapi and Burton, {Paul R.} and Toby Johnson and Adaikalavan Ramasamy and Zhao, {Jing Hua} and Guangju Zhai and Huffman, {Jennifer E.} and Veronique Vitart and Eva Albrecht and Wilmar Igl and Anna-Liisa Hartikainen and Anneli Pouta and Gemma Cadby and Jennie Hui and Palmer, {Lyle J.} and David Hadley and McArdle, {Wendy L.} and Rudnicka, {Alicja R.} and Ines Barroso and Loos, {Ruth J. F.} and Wareham, {Nicholas J.} and Massimo Mangino and Nicole Soranzo and Spector, {Tim D.} and Sven Glaeser and Georg Homuth and Henry Voelzke and Panos Deloukas and Raquel Granell and John Henderson and Ivica Grkovic and Stipan Jankovic and Lina Zgaga and Ozren Polasek and Igor Rudan and Wright, {Alan F.} and Harry Campbell and Wild, {Sarah H.} and Wilson, {James F.} and Joachim Heinrich and Medea Imboden and Probst-Hensch, {Nicole M.} and Ulf Gyllensten and Asa Johansson and Ghazal Zaboli and Linda Mustelin and Taina Rantanen and Ida Surakka and Jaakko Kaprio and Marjo-Riitta Jarvelin and Caroline Hayward and Evans, {David M.} and Beate Koch and Musk, {Arthur William} and Paul Elliott and Strachan, {David P.} and Tobin, {Martin D.} and Ian Sayers and Hall, {Ian P.}",

year = "2011",

doi = "10.1371/journal.pone.0019382",

language = "English",

volume = "6",

journal = "PL o S One ",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "5",

}

Obeidat, M, Wain, LV, Shrine, N, Kalsheker, N, Artigas, MS, Repapi, E, Burton, PR, Johnson, T, Ramasamy, A, Zhao, JH, Zhai, G, Huffman, JE, Vitart, V, Albrecht, E, Igl, W, Hartikainen, A-L, Pouta, A, Cadby, G, Hui, J, Palmer, LJ, Hadley, D, McArdle, WL, Rudnicka, AR, Barroso, I, Loos, RJF, Wareham, NJ, Mangino, M, Soranzo, N, Spector, TD, Glaeser, S, Homuth, G, Voelzke, H, Deloukas, P, Granell, R, Henderson, J, Grkovic, I, Jankovic, S, Zgaga, L, Polasek, O, Rudan, I, Wright, AF, Campbell, H, Wild, SH, Wilson, JF, Heinrich, J, Imboden, M, Probst-Hensch, NM, Gyllensten, U, Johansson, A, Zaboli, G, Mustelin, L, Rantanen, T, Surakka, I, Kaprio, J, Jarvelin, M-R, Hayward, C, Evans, DM, Koch, B, Musk, AW, Elliott, P, Strachan, DP, Tobin, MD, Sayers, I & Hall, IP 2011, 'A Comprehensive Evaluation of Potential Lung Function Associated Genes in the SpiroMeta General Population Sample', PL o S One , vol. 6, no. 5, e19382. https://doi.org/10.1371/journal.pone.0019382

TY - JOUR

T1 - A Comprehensive Evaluation of Potential Lung Function Associated Genes in the SpiroMeta General Population Sample

AU - Obeidat, Ma'en

AU - Wain, Louise V.

AU - Shrine, Nick

AU - Kalsheker, Noor

AU - Artigas, Maria Soler

AU - Repapi, Emmanouela

AU - Burton, Paul R.

AU - Johnson, Toby

AU - Ramasamy, Adaikalavan

AU - Zhao, Jing Hua

AU - Zhai, Guangju

AU - Huffman, Jennifer E.

AU - Vitart, Veronique

AU - Albrecht, Eva

AU - Igl, Wilmar

AU - Hartikainen, Anna-Liisa

AU - Pouta, Anneli

AU - Cadby, Gemma

AU - Hui, Jennie

AU - Palmer, Lyle J.

AU - Hadley, David

AU - McArdle, Wendy L.

AU - Rudnicka, Alicja R.

AU - Barroso, Ines

AU - Loos, Ruth J. F.

AU - Wareham, Nicholas J.

AU - Mangino, Massimo

AU - Soranzo, Nicole

AU - Spector, Tim D.

AU - Glaeser, Sven

AU - Homuth, Georg

AU - Voelzke, Henry

AU - Deloukas, Panos

AU - Granell, Raquel

AU - Henderson, John

AU - Grkovic, Ivica

AU - Jankovic, Stipan

AU - Zgaga, Lina

AU - Polasek, Ozren

AU - Rudan, Igor

AU - Wright, Alan F.

AU - Campbell, Harry

AU - Wild, Sarah H.

AU - Wilson, James F.

AU - Heinrich, Joachim

AU - Imboden, Medea

AU - Probst-Hensch, Nicole M.

AU - Gyllensten, Ulf

AU - Johansson, Asa

AU - Zaboli, Ghazal

AU - Mustelin, Linda

AU - Rantanen, Taina

AU - Surakka, Ida

AU - Kaprio, Jaakko

AU - Jarvelin, Marjo-Riitta

AU - Hayward, Caroline

AU - Evans, David M.

AU - Koch, Beate

AU - Musk, Arthur William

AU - Elliott, Paul

AU - Strachan, David P.

AU - Tobin, Martin D.

AU - Sayers, Ian

AU - Hall, Ian P.

PY - 2011

Y1 - 2011

N2 - Rationale: Lung function measures are heritable traits that predict population morbidity and mortality and are essential for the diagnosis of chronic obstructive pulmonary disease (COPD). Variations in many genes have been reported to affect these traits, but attempts at replication have provided conflicting results. Recently, we undertook a meta-analysis of Genome Wide Association Study (GWAS) results for lung function measures in 20,288 individuals from the general population (the SpiroMeta consortium). Objectives: To comprehensively analyse previously reported genetic associations with lung function measures, and to investigate whether single nucleotide polymorphisms (SNPs) in these genomic regions are associated with lung function in a large population sample. Methods: We analysed association for SNPs tagging 130 genes and 48 intergenic regions (+/-10 kb), after conducting a systematic review of the literature in the PubMed database for genetic association studies reporting lung function associations. Results: The analysis included 16,936 genotyped and imputed SNPs. No loci showed overall significant association for FEV1 or FEV1/FVC traits using a carefully defined significance threshold of 1.3 x 10(-5). The most significant loci associated with FEV1 include SNPs tagging MACROD2 (P = 6.81 x 10(-5)), CNTN5 (P = 4.37 x 10(-4)), and TRPV4 (P = 1.58 x 10(-3)). Among ever-smokers, SERPINA1 showed the most significant association with FEV1 (P = 8.41 x 10(-5)), followed by PDE4D (P = 1.22 x 10(-4)). The strongest association with FEV1/FVC ratio was observed with ABCC1 (P = 4.38 x 10(-4)), and ESR1 (P = 5.42 x 10(-4)) among ever-smokers. Conclusions: Polymorphisms spanning previously associated lung function genes did not show strong evidence for association with lung function measures in the SpiroMeta consortium population. Common SERPINA1 polymorphisms may affect FEV1 among smokers in the general population.

AB - Rationale: Lung function measures are heritable traits that predict population morbidity and mortality and are essential for the diagnosis of chronic obstructive pulmonary disease (COPD). Variations in many genes have been reported to affect these traits, but attempts at replication have provided conflicting results. Recently, we undertook a meta-analysis of Genome Wide Association Study (GWAS) results for lung function measures in 20,288 individuals from the general population (the SpiroMeta consortium). Objectives: To comprehensively analyse previously reported genetic associations with lung function measures, and to investigate whether single nucleotide polymorphisms (SNPs) in these genomic regions are associated with lung function in a large population sample. Methods: We analysed association for SNPs tagging 130 genes and 48 intergenic regions (+/-10 kb), after conducting a systematic review of the literature in the PubMed database for genetic association studies reporting lung function associations. Results: The analysis included 16,936 genotyped and imputed SNPs. No loci showed overall significant association for FEV1 or FEV1/FVC traits using a carefully defined significance threshold of 1.3 x 10(-5). The most significant loci associated with FEV1 include SNPs tagging MACROD2 (P = 6.81 x 10(-5)), CNTN5 (P = 4.37 x 10(-4)), and TRPV4 (P = 1.58 x 10(-3)). Among ever-smokers, SERPINA1 showed the most significant association with FEV1 (P = 8.41 x 10(-5)), followed by PDE4D (P = 1.22 x 10(-4)). The strongest association with FEV1/FVC ratio was observed with ABCC1 (P = 4.38 x 10(-4)), and ESR1 (P = 5.42 x 10(-4)) among ever-smokers. Conclusions: Polymorphisms spanning previously associated lung function genes did not show strong evidence for association with lung function measures in the SpiroMeta consortium population. Common SERPINA1 polymorphisms may affect FEV1 among smokers in the general population.

U2 - 10.1371/journal.pone.0019382

DO - 10.1371/journal.pone.0019382

M3 - Article

SN - 1932-6203

VL - 6

JO - PL o S One

JF - PL o S One

IS - 5

M1 - e19382

ER -

A Comprehensive Evaluation of Potential Lung Function Associated Genes in the SpiroMeta General Population Sample

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