Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Targeted high-throughput sequencing of candidate genes for chronic obstructive pulmonary disease
Karolinska Inst, Dept Biosci & Nutr, SE-14183 Huddinge, Sweden.;Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
Karolinska Inst, Dept Biosci & Nutr, SE-14183 Huddinge, Sweden.;Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
Karolinska Inst, Dept Biosci & Nutr, SE-14183 Huddinge, Sweden.;Univ Helsinki, Mol Neurol Res Program, Helsinki, Finland.;Univ Helsinki, Folkhalsan Inst Genet, Helsinki, Finland..
Inst Univ Cardiol & Pneumol Quebec, Ville De Quebec, PQ, Canada..
Show others and affiliations
2016 (English)In: BMC Pulmonary Medicine, ISSN 1471-2466, E-ISSN 1471-2466, Vol. 16, article id 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, article id 146
Keyword [en]
COPD, Sequencing, eQTL, Association, Lung development, CHRNA5
National Category
Respiratory Medicine and Allergy
Identifiers
URN: urn:nbn:se:uu:diva-311194DOI: 10.1186/s12890-016-0309-yISI: 000388035500004PubMedID: 27835950OAI: oai:DiVA.org:uu-311194DiVA, id: diva2:1059183
Funder
Swedish Society for Medical Research (SSMF)Magnus Bergvall Foundation, 014-00163
Available from: 2016-12-22 Created: 2016-12-22 Last updated: 2017-11-29Bibliographically approved

Open Access in DiVA

fulltext(764 kB)53 downloads
File information
File name FULLTEXT01.pdfFile size 764 kBChecksum SHA-512
6be15d2e740b692188c920291c06ea251a23cdac4d6d236f168a20b4a494d555e85df6328bdd26d6d96b4b02cd8a6710a84f84a5c8f119c4b51bdf9e53ec2a57
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Gudmundsson, SannaKlar, Joakim
By organisation
Medicinsk genetik och genomikScience for Life Laboratory, SciLifeLab
In the same journal
BMC Pulmonary Medicine
Respiratory Medicine and Allergy

Search outside of DiVA

GoogleGoogle Scholar
Total: 53 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

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 313 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf