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

Obeidat, M; Wain, LV; Shrine, N; Kalsheker, N; Soler Artigas, M; Repapi, E; Burton, PR; Johnson, T; Ramasamy, A; Zhao, JH; et al. Obeidat, M; Wain, LV; Shrine, N; Kalsheker, N; Soler Artigas, M; Repapi, E; Burton, PR; Johnson, T; Ramasamy, A; Zhao, JH; Zhai, G; Huffman, JE; Vitart, V; Albrecht, E; Igl, W; Hartikainen, AL; Pouta, A; Cadby, G; Hui, J; Palmer, LJ; Hadley, D; McArdle, WL; Rudnicka, AR; Barroso, I; Loos, RJ; Wareham, NJ; Mangino, M; Soranzo, N; Spector, TD; Gläser, S; Homuth, G; Völzke, H; Deloukas, P; Granell, R; Henderson, J; Grkovic, I; Jankovic, S; Zgaga, L; Polašek, O; Rudan, I; Wright, AF; Campbell, H; Wild, SH; Wilson, JF; Heinrich, J; Imboden, M; Probst-Hensch, NM; Gyllensten, U; Johansson, Å; Zaboli, G; Mustelin, L; Rantanen, T; Surakka, I; Kaprio, J; Jarvelin, MR; Hayward, C; Evans, DM; Koch, B; Musk, AW; Elliott, P; Strachan, DP; Tobin, MD; Sayers, I; Hall, IP; SpiroMeta Consortium, (2011) A Comprehensive Evaluation of Potential Lung Function Associated Genes in the SpiroMeta General Population Sample. PLOS ONE, 6 (5). e19382 (1) - e19382 (9). ISSN 1932-6203 https://doi.org/10.1371/journal.pone.0019382
SGUL Authors: Rudnicka, Alicja Regina Strachan, David Peter

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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 (+/210 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 1.361025. The most significant loci associated with FEV1 include SNPs tagging MACROD2 (P = 6.8161025), CNTN5 (P = 4.3761024), and TRPV4 (P = 1.5861023). Among eversmokers, SERPINA1 showed the most significant association with FEV1 (P = 8.4161025), followed by PDE4D (P = 1.2261024). The strongest association with FEV1/FVC ratio was observed with ABCC1 (P = 4.3861024), and ESR1 (P = 5.4261024) 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.

Item Type: Article
Additional Information: 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
Keywords: Biological Markers, Forced Expiratory Volume, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, Great Britain, Humans, Lung, Meta-Analysis as Topic, Polymorphism, Single Nucleotide, Pulmonary Disease, Chronic Obstructive, Respiratory Function Tests, Vital Capacity, Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, MULTIDISCIPLINARY SCIENCES, OBSTRUCTIVE PULMONARY-DISEASE, PHOSPHODIESTERASE 4D GENE, ALPHA(1)-ANTITRYPSIN DEFICIENCY, HEALTH, PDE4D, RISK
SGUL Research Institute / Research Centre: Academic Structure > Population Health Research Institute (INPH)
Journal or Publication Title: PLOS ONE
ISSN: 1932-6203
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Dates:
DateEvent
20 May 2011Published
Web of Science ID: WOS:000290793400003
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URI: http://openaccess.sgul.ac.uk/id/eprint/1841
Publisher's version: https://doi.org/10.1371/journal.pone.0019382

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