Genetics of sputum gene expression in chronic obstructive pulmonary disease

Weiliang Qiu, Michael H. Cho, John H. Riley, Wayne H. Anderson, Dave Singh, Per Bakke, Amund Gulsvik, Augusto A. Litonjua, David A. Lomas, James D. Crapo, Terri H. Beaty, Bartolome R. Celli, Stephen Rennard, Ruth Tal-Singer, Steven M. Fox, Edwin K. Silverman, Craig P. Hersh

Research output: Contribution to journalArticle

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Abstract

Previous expression quantitative trait loci (eQTL) studies have performed genetic association studies for gene expression, but most of these studies examined lymphoblastoid cell lines from non-diseased individuals. We examined the genetics of gene expression in a relevant disease tissue from chronic obstructive pulmonary disease (COPD) patients to identify functional effects of known susceptibility genes and to find novel disease genes. By combining gene expression profiling on induced sputum samples from 131 COPD cases from the ECLIPSE Study with genomewide single nucleotide polymorphism (SNP) data, we found 4315 significant cis-eQTL SNP-probe set associations (3309 unique SNPs). The 3309 SNPs were tested for association with COPD in a genomewide association study (GWAS) dataset, which included 2940 COPD cases and 1380 controls. Adjusting for 3309 tests (p<1.5e-5), the two SNPs which were significantly associated with COPD were located in two separate genes in a known COPD locus on chromosome 15: CHRNA5 and IREB2. Detailed analysis of chromosome 15 demonstrated additional eQTLs for IREB2 mapping to that gene. eQTL SNPs for CHRNA5 mapped to multiple linkage disequilibrium (LD) bins. The eQTLs for IREB2 and CHRNA5 were not in LD. Seventy-four additional eQTL SNPs were associated with COPD at p<0.01. These were genotyped in two COPD populations, finding replicated associations with a SNP in PSORS1C1, in the HLA-C region on chromosome 6. Integrative analysis of GWAS and gene expression data from relevant tissue from diseased subjects has located potential functional variants in two known COPD genes and has identified a novel COPD susceptibility locus.

Original languageEnglish (US)
Article numbere24395
JournalPloS one
Volume6
Issue number9
DOIs
StatePublished - Sep 16 2011

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Pulmonary diseases
Sputum
Gene expression
respiratory tract diseases
Chronic Obstructive Pulmonary Disease
Single Nucleotide Polymorphism
Gene Expression
gene expression
Quantitative Trait Loci
Genes
quantitative trait loci
Chromosomes
Polymorphism
single nucleotide polymorphism
Chromosomes, Human, Pair 15
Nucleotides
Linkage Disequilibrium
linkage disequilibrium
genes
Genetics

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Qiu, W., Cho, M. H., Riley, J. H., Anderson, W. H., Singh, D., Bakke, P., ... Hersh, C. P. (2011). Genetics of sputum gene expression in chronic obstructive pulmonary disease. PloS one, 6(9), [e24395]. https://doi.org/10.1371/journal.pone.0024395

Genetics of sputum gene expression in chronic obstructive pulmonary disease. / Qiu, Weiliang; Cho, Michael H.; Riley, John H.; Anderson, Wayne H.; Singh, Dave; Bakke, Per; Gulsvik, Amund; Litonjua, Augusto A.; Lomas, David A.; Crapo, James D.; Beaty, Terri H.; Celli, Bartolome R.; Rennard, Stephen; Tal-Singer, Ruth; Fox, Steven M.; Silverman, Edwin K.; Hersh, Craig P.

In: PloS one, Vol. 6, No. 9, e24395, 16.09.2011.

Research output: Contribution to journalArticle

Qiu, W, Cho, MH, Riley, JH, Anderson, WH, Singh, D, Bakke, P, Gulsvik, A, Litonjua, AA, Lomas, DA, Crapo, JD, Beaty, TH, Celli, BR, Rennard, S, Tal-Singer, R, Fox, SM, Silverman, EK & Hersh, CP 2011, 'Genetics of sputum gene expression in chronic obstructive pulmonary disease', PloS one, vol. 6, no. 9, e24395. https://doi.org/10.1371/journal.pone.0024395
Qiu W, Cho MH, Riley JH, Anderson WH, Singh D, Bakke P et al. Genetics of sputum gene expression in chronic obstructive pulmonary disease. PloS one. 2011 Sep 16;6(9). e24395. https://doi.org/10.1371/journal.pone.0024395
Qiu, Weiliang ; Cho, Michael H. ; Riley, John H. ; Anderson, Wayne H. ; Singh, Dave ; Bakke, Per ; Gulsvik, Amund ; Litonjua, Augusto A. ; Lomas, David A. ; Crapo, James D. ; Beaty, Terri H. ; Celli, Bartolome R. ; Rennard, Stephen ; Tal-Singer, Ruth ; Fox, Steven M. ; Silverman, Edwin K. ; Hersh, Craig P. / Genetics of sputum gene expression in chronic obstructive pulmonary disease. In: PloS one. 2011 ; Vol. 6, No. 9.
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