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

被引：48

作者：

Obeidat, Ma'en ^{[1
]}

Wain, Louise V. ^{[2
,3
]}

Shrine, Nick ^{[2
,3
]}

Kalsheker, Noor ^{[4
,5
]}

Artigas, Maria Soler ^{[2
,3
]}

Repapi, Emmanouela ^{[2
,3
,6
]}

Burton, Paul R. ^{[2
,3
]}

Johnson, Toby ^{[7
]}

Ramasamy, Adaikalavan ^{[8
,9
]}

Zhao, Jing Hua ^{[10
]}

Zhai, Guangju ^{[11
]}

Huffman, Jennifer E. ^{[12
]}

Vitart, Veronique ^{[12
]}

Albrecht, Eva ^{[13
]}

Igl, Wilmar ^{[14
]}

Hartikainen, Anna-Liisa ^{[15
]}

Pouta, Anneli ^{[16
]}

Cadby, Gemma ^{[17
,18
]}

Hui, Jennie ^{[19
,20
,21
,22
]}

Palmer, Lyle J. ^{[17
,18
]}

Hadley, David ^{[23
,24
]}

McArdle, Wendy L. ^{[25
]}

Rudnicka, Alicja R. ^{[23
]}

Barroso, Ines ^{[26
,27
]}

Loos, Ruth J. F. ^{[10
]}

Wareham, Nicholas J. ^{[10
]}

Mangino, Massimo ^{[11
]}

Soranzo, Nicole ^{[11
,26
]}

Spector, Tim D. ^{[11
]}

Glaeser, Sven ^{[28
]}

Homuth, Georg ^{[29
]}

Voelzke, Henry ^{[30
]}

Deloukas, Panos ^{[26
]}

Granell, Raquel

Henderson, John

Grkovic, Ivica ^{[31
]}

Jankovic, Stipan ^{[31
]}

Zgaga, Lina ^{[32
]}

Polasek, Ozren ^{[33
]}

Rudan, Igor ^{[31
,34
]}

Wright, Alan F. ^{[12
]}

Campbell, Harry ^{[34
]}

Wild, Sarah H. ^{[34
]}

Wilson, James F. ^{[34
]}

Heinrich, Joachim ^{[51
]}

Imboden, Medea ^{[35
]}

Probst-Hensch, Nicole M. ^{[35
,36
]}

Gyllensten, Ulf ^{[37
]}

Johansson, Asa ^{[37
]}

Zaboli, Ghazal ^{[14
]}

机构：

[1] Univ Nottingham Hosp, Div Therapeut & Mol Med, Nottingham Resp Biomed Res Unit, Nottingham NG7 2UH, England

[2] Univ Leicester, Dept Hlth Sci, Leicester, Leics, England

[3] Univ Leicester, Dept Genet, Leicester LE1 7RH, Leics, England

[4] Univ Nottingham, Sch Mol Med Sci, Nottingham NG7 2RD, England

[5] Univ Nottingham, Queens Med Ctr, Ctr Genet & Genom, Nottingham NG7 2RD, England

[6] Univ Oxford, Ludwig Inst Canc Res, Oxford, England

[7] Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England

[8] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Resp Epidemiol & Publ Hlth Grp, London, England

[9] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England

[10] Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England

[11] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England

[12] Western Gen Hosp, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland

[13] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany

[14] Uppsala Univ, Dept Genet & Pathol, Rudbeck Lab, Uppsala, Sweden

[15] Univ Oulu, Inst Clin Med, Dept Clin Sci Obstet & Gynecol, Oulu, Finland

[16] Natl Inst Hlth & Welf, Dept Life Course & Serv, Oulu, Finland

[17] Ontario Inst Canc Res, Toronto, ON, Canada

[18] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada

[19] PathWest Lab Med WA, Nedlands, WA, Australia

[20] Sir Charles Gairdner Hosp, Busselton Populat Med Res Fdn, Nedlands, WA 6009, Australia

[21] Univ Western Australia, Sch Populat Hlth, Crawley, Australia

[22] Univ Western Australia, Sch Pathol & Lab Med, Crawley, Australia

[23] St Georges Univ London, Div Community Hlth Sci, London, England

[24] Univ S Florida, Pediat Epidemiol Ctr, Tampa, FL USA

[25] Univ Bristol, Sch Social & Community Med, ALSPAC Lab, Bristol, Avon, England

[26] Wellcome Trust Sanger Inst, Cambridge, England

[27] Univ Cambridge, Metab Res Labs, Inst Metab Sci, Addenbrookes Hosp Cambridge, Cambridge, England

[28] Ernst Moritz Arndt Univ Greifswald, Dept Internal Med Cardiol Intens Care Pulm Med &, Greifswald, Germany

[29] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany

[30] Ernst Moritz Arndt Univ Greifswald, SHIP Clin Epidemiol Res, Inst Community Med, Greifswald, Germany

[31] Univ Split, Sch Med, Croatian Ctr Global Hlth, Split, Croatia

[32] Univ Zagreb, Fac Med, Andrija Stampar Sch Publ Hlth, Zagreb 41000, Croatia

[33] Univ Split, Dept Publ Hlth, Split, Croatia

[34] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland

[35] Univ Basel, Basel, Switzerland

[36] Swiss Trop & Publ Hlth Inst, Basel, Switzerland

[37] Uppsala Univ, Dept Immunol Genet & Pathol, Rudbeck Lab, Uppsala, Sweden

[38] Univ Helsinki, Dept Publ Hlth, Helsinki, Finland

[39] Univ Jyvaskyla, Dept Hlth Sci, Jyvaskyla, Finland

[40] Univ Jyvaskyla, Gerontol Res Ctr, Jyvaskyla, Finland

[41] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland

[42] Natl Inst Hlth & Welf, Helsinki, Finland

[43] Univ Oulu, Inst Hlth Sci, Oulu, Finland

[44] Univ Oulu, Bioctr Oulu, Oulu, Finland

[45] Univ Bristol, Sch Social & Community Med, MRC Ctr Causal Anal Translat Epidemiol, Bristol, Avon, England

[46] Sir Charles Gairdner Hosp, Dept Resp Med, Nedlands, WA 6009, Australia

[47] Univ Western Australia, Sch Med, Crawley, Australia

[48] Univ London Imperial Coll Sci Technol & Med, MRC HPA Ctr Environm & Hlth, London, England

[49] SpiroMeta Consortium, Leicester, Leics, England

[50] Univ Western Australia, Sch Pharmacol, Crawley, Australia

来源：

PLOS ONE | 2011年 / 6卷 / 05期

基金：

英国医学研究理事会; 英国生物技术与生命科学研究理事会; 英国惠康基金; 芬兰科学院;

关键词：

OBSTRUCTIVE PULMONARY-DISEASE; PHOSPHODIESTERASE 4D GENE; ALPHA(1)-ANTITRYPSIN DEFICIENCY; HEALTH; PDE4D; RISK;

D O I：

10.1371/journal.pone.0019382

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 FEV(1) or FEV(1)/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.

引用

页数：9

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