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

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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 , Palmer , L J , Hadley , D , McArdle , W L , Rudnicka , A R , Barroso , I , Loos , R J F , Wareham , N J , Mangino , M , Soranzo , N , Spector , T D , Glaeser , S , Homuth , G , Voelzke , H , Deloukas , P , Granell , R , Henderson , J , Grkovic , I , Jankovic , S , Zgaga , L , Polasek , O , Rudan , I , Wright , A F , Campbell , H , Wild , S H , Wilson , J F , Heinrich , J , Imboden , M , Probst-Hensch , N M , Mustelin , L , Surakka , I , Kaprio , J & SpiroMeta Consortium 2011 , ' A Comprehensive Evaluation of Potential Lung Function Associated Genes in the SpiroMeta General Population Sample ' , PLoS One , vol. 6 , no. 5 , pp. - . https://doi.org/10.1371/journal.pone.0019382

Title: A Comprehensive Evaluation of Potential Lung Function Associated Genes in the SpiroMeta General Population Sample
Author: Obeidat, Ma'en; Wain, Louise V.; Shrine, Nick; Kalsheker, Noor; Artigas, Maria Soler; Repapi, Emmanouela; Burton, Paul R.; Johnson, Toby; Ramasamy, Adaikalavan; Zhao, Jing Hua; Zhai, Guangju; Huffman, Jennifer E.; Vitart, Veronique; Albrecht, Eva; Igl, Wilmar; Hartikainen, Anna-Liisa; Pouta, Anneli; Cadby, Gemma; Hui, Jennie; Palmer, Lyle J.; Hadley, David; McArdle, Wendy L.; Rudnicka, Alicja R.; Barroso, Ines; Loos, Ruth J. F.; Wareham, Nicholas J.; Mangino, Massimo; Soranzo, Nicole; Spector, Tim D.; Glaeser, Sven; Homuth, Georg; Voelzke, Henry; Deloukas, Panos; Granell, Raquel; Henderson, John; Grkovic, Ivica; Jankovic, Stipan; Zgaga, Lina; Polasek, Ozren; Rudan, Igor; Wright, Alan F.; Campbell, Harry; Wild, Sarah H.; Wilson, James F.; Heinrich, Joachim; Imboden, Medea; Probst-Hensch, Nicole M.; Mustelin, Linda; Surakka, Ida; Kaprio, Jaakko; SpiroMeta Consortium
Contributor organization: Department of Public Health
Institute for Molecular Medicine Finland
Genetic Epidemiology
Date: 2011
Language: eng
Number of pages: 9
Belongs to series: PLoS One
ISSN: 1932-6203
DOI: https://doi.org/10.1371/journal.pone.0019382
URI: http://hdl.handle.net/10138/165660
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 FEV(1) or FEV(1)/FVC traits using a carefully defined significance threshold of 1.3×10(-5). The most significant loci associated with FEV(1) include SNPs tagging MACROD2 (P = 6.81×10(-5)), CNTN5 (P = 4.37×10(-4)), and TRPV4 (P = 1.58×10(-3)). Among ever-smokers, SERPINA1 showed the most significant association with FEV(1) (P = 8.41×10(-5)), followed by PDE4D (P = 1.22×10(-4)). The strongest association with FEV(1)/FVC ratio was observed with ABCC1 (P = 4.38×10(-4)), and ESR1 (P = 5.42×10(-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 FEV(1) among smokers in the general population.
Subject: OBSTRUCTIVE PULMONARY-DISEASE
PHOSPHODIESTERASE 4D GENE
ALPHA(1)-ANTITRYPSIN DEFICIENCY
HEALTH
PDE4D
RISK
3142 Public health care science, environmental and occupational health
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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