umu.sePublications
Change search
ReferencesLink to record
Permanent link

Direct link
Targeted high-throughput sequencing of candidate genes for chronic obstructive pulmonary disease
Show others and affiliations
2016 (English)In: BMC Pulmonary Medicine, ISSN 1471-2466, E-ISSN 1471-2466, Vol. 16, 146Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Reduced lung function in patients with chronic obstructive pulmonary disease (COPD) is likely due to both environmental and genetic factors. We report here a targeted high-throughput DNA sequencing approach to identify new and previously known genetic variants in a set of candidate genes for COPD.

METHODS: Exons in 22 genes implicated in lung development as well as 61 genes and 10 genomic regions previously associated with COPD were sequenced using individual DNA samples from 68 cases with moderate or severe COPD and 66 controls matched for age, gender and smoking. Cases and controls were selected from the Obstructive Lung Disease in Northern Sweden (OLIN) studies.

RESULTS: In total, 37 genetic variants showed association with COPD (p < 0.05, uncorrected). Several variants previously discovered to be associated with COPD from genetic genome-wide analysis studies were replicated using our sample. Two high-risk variants were followed-up for functional characterization in a large eQTL mapping study of 1,111 human lung specimens. The C allele of a synonymous variant, rs8040868, predicting a p.(S45=) in the gene for cholinergic receptor nicotinic alpha 3 (CHRNA3) was associated with COPD (p = 8.8 x 10(-3)). This association remained (p = 0.003 and OR = 1.4, 95 % CI 1.1-1.7) when analysing all available cases and controls in OLIN (n = 1,534). The rs8040868 variant is in linkage disequilibrium with rs16969968 previously associated with COPD and altered expression of the CHRNA5 gene. A follow-up analysis for detection of expression quantitative trait loci revealed that rs8040868-C was found to be significantly associated with a decreased expression of the nearby gene cholinergic receptor, nicotinic, alpha 5 (CHRNA5) in lung tissue.

CONCLUSION: Our data replicate previous result suggesting CHRNA5 as a candidate gene for COPD and rs8040868 as a risk variant for the development of COPD in the Swedish population.

Place, publisher, year, edition, pages
2016. Vol. 16, 146
Keyword [en]
COPD, Sequencing, eQTL, Association, Lung development, CHRNA5
National Category
Environmental Health and Occupational Health
Identifiers
URN: urn:nbn:se:umu:diva-128112DOI: 10.1186/s12890-016-0309-yISI: 000388035500004PubMedID: 27835950ScopusID: 2-s2.0-84995466776OAI: oai:DiVA.org:umu-128112DiVA: diva2:1049081
Available from: 2016-11-23 Created: 2016-11-23 Last updated: 2016-12-30Bibliographically approved

Open Access in DiVA

fulltext(1546 kB)14 downloads
File information
File name FULLTEXT01.pdfFile size 1546 kBChecksum SHA-512
e7096ed6ab3a6cb79a58d66d70aee881cb67389b9d2d85cc3981396fe0307090d5787c8aa29d61540068d322cc57e4f836a41d8cae1990af6105ec87d4618e84
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMedScopus

Search in DiVA

By author/editor
Backman, HelenaLindberg, AnneRönmark, Eva
By organisation
Occupational and Environmental MedicineMedicine
In the same journal
BMC Pulmonary Medicine
Environmental Health and Occupational Health

Search outside of DiVA

GoogleGoogle Scholar
Total: 14 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 2 hits
ReferencesLink to record
Permanent link

Direct link