Year: 2011
Type: article
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.
Source: PLoS ONE
Authors: 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, and the ECLIPSE Investigators
Institutions: Brigham and Women's Hospital, Harvard University, GlaxoSmithKline (United Kingdom), University of Manchester, Medicines Evaluation Unit, Haukeland University Hospital, University of Bergen, University of Cambridge, National Jewish Health, Johns Hopkins University, University of Nebraska Medical Center, GlaxoSmithKline (United States)
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,382
Awards: CLINICAL CENTER FOR THE LUNG VOLUME REDUCTION SURGERY, G1207659464, G1220799682, LUNG VOLUME REDUCTION STUDY--CLINICAL CENTER, LONG-TERM OXYGEN TREATMENT TRIAL (LOTT) PHARMACOGENOMICS ANCILLARY STUDY, G1439225947, G1576662596, G1605453878, G1615620936, G1617588125, CLINICAL CENTER FOR LVRS, G1735610881, CLNICAL CENTER FOR LVRS, CLNICAL CENTER FOR LVRS, Fine Mapping of a COPD Locus on Chromosome 19q, G182694510, LUNG VOLUME REDUCTION STUDY--CLINICAL CENTER, LUNG VOLUME REDUCTION SURGERY--CLINICAL CENTER, LUNG VOLUME REDUCTION SURGERY--CLINICAL CENTER, G2412257637, LUNG VOLUME REDUCTION SURGERY--CLINICAL CENTER, LUNG VOLUME REDUCTION SURGERY--CLINICAL CENTER, G2599011918, G278468722, G3110798224, G3146753889, CLINICAL COORDINATING CENTER FOR LVRS, G3715945925, G3805264881, G3874500373, G4153249725, Genetic Determinants of COPD in Diverse Ethnic Groups, G4255341634, G468516202, G48533833, G5181772611, G520825964, G5484345081, G556935766, (2 of 2) Genetic Epidemiology of COPD, G5791858519, G6315211796, CLNICAL CENTER FOR THE LVRS, G6570314638, LUNG VOLUME REDUCTION SURGERY--CLINICAL CENTER, CLINICAL CENTER FOR LVRS, (1 of 2) Genetic Epidemiology of COPD, CLINICAL CENTER FOR THE LUNG VOLUME REDUCTION SURGERY, G6996658085, G7092741763, G7218825848, G7541302268, G754838926, G7669442478, Approaches to Identify Rare and Common Genetic Determinants in Severe COPD, G778147052, Common Genetic Determinants of Asthma and COPD-PROGRAM PROJECT, G7949433598, G8081622010, G8938195782, LUNG VOLUME REDUCTION SURGERY--CLINICAL CENTER, CLINICAL CENTER FOR THE LUNG VOLUME REDUCTION SURGERY, CLINICAL CENTER FOR THE LUNG VOLUME REDUCTION SURGERY, G943488547
OpenAlex ID: W2074127159