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Title: A comprehensive evaluation of potential lung function associated genes in the SpiroMeta general population sample.
Authors: Obeidat, Ma'en
Wain, Louise V.
Shrine, Nick
Kalsheker, Noor
Soler Artigas, Maria
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, Inês
Loos, Ruth J.F.
Wareham, Nicholas J
Mangino, Massimo
Soranzo, Nicole
Spector, Tim D.
Gläser, Sven
Homuth, Georg
Völzke, Henry
Deloukas, Panos
Granell, Raquel
Henderson, John
Grkovic, Ivica
Jankovic, Stipan
Zgaga, Lina
Polašek, Ozren
Rudan, Igor
Wright, Alan F.
Campbell, Harry
Wild, Sarah H.
Wilson, James F.
Heinrich, Joachim
Imboden, Medea
Probst-Hensch, Nicole M.
Gyllensten, Ulf
Johansson, Åsa
Zaboli, Ghazal
Mustelin, Linda
Rantanen, Taina
Surakka, Ida
Kaprio, Jaakko
Jarvelin, Marjo-Riitta
Hayward, Caroline
Evans, David M.
Koch, Beate
Musk, Arthur William
Elliott, Paul
Strachan, David P.
Tobin, Martin D.
Sayers, Ian
Hall, Ian P.
SpiroMeta Consortium
First Published: 20-May-2011
Publisher: Public Library of Science
Citation: PLoS One, 2011, 6 (5), e19382.
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 1.3×10−5. The most significant loci associated with FEV1 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 FEV1 (P = 8.41×10−5), followed by PDE4D (P = 1.22×10−4). The strongest association with FEV1/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 FEV1 among smokers in the general population.
DOI Link: 10.1371/journal.pone.0019382
ISSN: 1932-6203
eISSN: 1932-6203
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright: © 2011 Obeidat et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Appears in Collections:Published Articles, Dept. of Health Sciences

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