Targeted high-throughput sequencing of candidate genes for chronic obstructive pulmonary disease
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...
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Umeå universitet, Yrkes- och miljömedicin
2016
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Online Access: | http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-128112 https://doi.org/10.1186/s12890-016-0309-y |
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ftumeauniv:oai:DiVA.org:umu-128112 2024-02-11T10:07:12+01:00 Targeted high-throughput sequencing of candidate genes for chronic obstructive pulmonary disease Matsson, Hans Söderhäll, Cilla Einarsdottir, Elisabet Lamontagne, Maxime Gudmundsson, Sanna Backman, Helena Lindberg, Anne Rönmark, Eva Kere, Juha Sin, Don Postma, Dirkje S Bossé, Yohan Lundbäck, Bo Klar, Joakim 2016 application/pdf http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-128112 https://doi.org/10.1186/s12890-016-0309-y eng eng Umeå universitet, Yrkes- och miljömedicin Umeå universitet, Medicin BMC Pulmonary Medicine, 2016, 16, http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-128112 doi:10.1186/s12890-016-0309-y PMID 27835950 ISI:000388035500004 Scopus 2-s2.0-84995466776 info:eu-repo/semantics/openAccess COPD Sequencing eQTL Association Lung development CHRNA5 Occupational Health and Environmental Health Arbetsmedicin och miljömedicin Article in journal info:eu-repo/semantics/article text 2016 ftumeauniv https://doi.org/10.1186/s12890-016-0309-y 2024-01-17T23:36:34Z 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. Article in Journal/Newspaper Northern Sweden Umeå University: Publications (DiVA) BMC Pulmonary Medicine 16 1 |
institution |
Open Polar |
collection |
Umeå University: Publications (DiVA) |
op_collection_id |
ftumeauniv |
language |
English |
topic |
COPD Sequencing eQTL Association Lung development CHRNA5 Occupational Health and Environmental Health Arbetsmedicin och miljömedicin |
spellingShingle |
COPD Sequencing eQTL Association Lung development CHRNA5 Occupational Health and Environmental Health Arbetsmedicin och miljömedicin Matsson, Hans Söderhäll, Cilla Einarsdottir, Elisabet Lamontagne, Maxime Gudmundsson, Sanna Backman, Helena Lindberg, Anne Rönmark, Eva Kere, Juha Sin, Don Postma, Dirkje S Bossé, Yohan Lundbäck, Bo Klar, Joakim Targeted high-throughput sequencing of candidate genes for chronic obstructive pulmonary disease |
topic_facet |
COPD Sequencing eQTL Association Lung development CHRNA5 Occupational Health and Environmental Health Arbetsmedicin och miljömedicin |
description |
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. |
format |
Article in Journal/Newspaper |
author |
Matsson, Hans Söderhäll, Cilla Einarsdottir, Elisabet Lamontagne, Maxime Gudmundsson, Sanna Backman, Helena Lindberg, Anne Rönmark, Eva Kere, Juha Sin, Don Postma, Dirkje S Bossé, Yohan Lundbäck, Bo Klar, Joakim |
author_facet |
Matsson, Hans Söderhäll, Cilla Einarsdottir, Elisabet Lamontagne, Maxime Gudmundsson, Sanna Backman, Helena Lindberg, Anne Rönmark, Eva Kere, Juha Sin, Don Postma, Dirkje S Bossé, Yohan Lundbäck, Bo Klar, Joakim |
author_sort |
Matsson, Hans |
title |
Targeted high-throughput sequencing of candidate genes for chronic obstructive pulmonary disease |
title_short |
Targeted high-throughput sequencing of candidate genes for chronic obstructive pulmonary disease |
title_full |
Targeted high-throughput sequencing of candidate genes for chronic obstructive pulmonary disease |
title_fullStr |
Targeted high-throughput sequencing of candidate genes for chronic obstructive pulmonary disease |
title_full_unstemmed |
Targeted high-throughput sequencing of candidate genes for chronic obstructive pulmonary disease |
title_sort |
targeted high-throughput sequencing of candidate genes for chronic obstructive pulmonary disease |
publisher |
Umeå universitet, Yrkes- och miljömedicin |
publishDate |
2016 |
url |
http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-128112 https://doi.org/10.1186/s12890-016-0309-y |
genre |
Northern Sweden |
genre_facet |
Northern Sweden |
op_relation |
BMC Pulmonary Medicine, 2016, 16, http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-128112 doi:10.1186/s12890-016-0309-y PMID 27835950 ISI:000388035500004 Scopus 2-s2.0-84995466776 |
op_rights |
info:eu-repo/semantics/openAccess |
op_doi |
https://doi.org/10.1186/s12890-016-0309-y |
container_title |
BMC Pulmonary Medicine |
container_volume |
16 |
container_issue |
1 |
_version_ |
1790605355874516992 |