A comprehensive evaluation of potential lung function associated genes in the SpiroMeta general population sample

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., Glaser, Sven, Homuth, Georg, Volzke, 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., Gyllensten, Ulf, Johansson, Asa, 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. and 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. doi:10.1371/journal.pone.0019382

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
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.
Glaser, Sven
Homuth, Georg
Volzke, 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.
Gyllensten, Ulf
Johansson, Asa
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
Title A comprehensive evaluation of potential lung function associated genes in the SpiroMeta general population sample
Journal name PLoS ONE   Check publisher's open access policy
ISSN 1932-6203
Publication date 2011-05-01
Year available 2011
Sub-type Article (original research)
DOI 10.1371/journal.pone.0019382
Open Access Status DOI
Volume 6
Issue 5
Start page e19382.1
End page e19382.9
Total pages 9
Place of publication San Francisco United States
Publisher Public Library of Science (PLoS)
Language eng
Formatted abstract
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).

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.

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.

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.

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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 40 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 40 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Thu, 13 Mar 2014, 20:13:37 EST by System User on behalf of School of Medicine