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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50 Citations (Scopus)


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 languageEnglish
Article numbere19382
JournalPL o S One
Issue number5
Publication statusPublished - 2011


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