Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/88539
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
Title: | A comprehensive evaluation of potential lung function associated genes in the SpiroMeta general population sample |
Author: | Obeidat, M. Wain, L. Shrine, N. Kalsheker, N. Soler Artigas, M. Repapi, E. Burton, P. Johnson, T. Ramasamy, A. Zhao, J.-H. Zhai, G. Huffman, J. Vitart, V. Albrecht, E. Igl, W. Hartikainen, A.-L. Pouta, A. Cadby, G. Hui, J. Palmer, L. et al. |
Citation: | PLoS One, 2011; 6(5):e19382-online |
Publisher: | Public Library of Science |
Issue Date: | 2011 |
ISSN: | 1932-6203 1932-6203 |
Editor: | Semple, M.G. |
Statement of Responsibility: | Ma’en Obeidat ... Lyle J. Palmer ... SpiroMeta Consortium ... et al. |
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. |
Keywords: | SpiroMeta Consortium Lung Humans Pulmonary Disease, Chronic Obstructive Genetic Predisposition to Disease Respiratory Function Tests Vital Capacity Forced Expiratory Volume Polymorphism, Single Nucleotide Genome, Human Meta-Analysis as Topic Genome-Wide Association Study Biomarkers United Kingdom |
Rights: | © 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. |
DOI: | 10.1371/journal.pone.0019382 |
Grant ID: | U01 DK062418 |
Published version: | http://dx.doi.org/10.1371/journal.pone.0019382 |
Appears in Collections: | Aurora harvest 7 Translational Health Science publications |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
hdl_88539.pdf | Published version | 444.16 kB | Adobe PDF | View/Open |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.