A Whole-Blood Transcriptome Meta-Analysis Identifies Gene Expression Signatures of Cigarette Smoking.

2.50
Hdl Handle:
http://hdl.handle.net/11287/619957
Title:
A Whole-Blood Transcriptome Meta-Analysis Identifies Gene Expression Signatures of Cigarette Smoking.
Authors:
Huan, T.; Joehanes, R.; Schurmann, C.; Schramm, K.; Pilling, L. C.; Peters, M. J.; Mägi, R.; DeMeo, D.; O'Connor, G. T.; Ferrucci, L.; Teumer, A.; Homuth, G.; Biffar, R.; Völker, U.; Herder, C.; Waldenberger, M.; Peters, A.; Zeilinger, S.; Metspalu, A.; Hofman, A.; Uitterlinden, A. G.; Hernandez, D. G.; Singleton, A. B.; Bandinelli, S.; Munson, P. J.; Lin, Ho.; Benjamin, E.J.; Esko, T.; Grabe, H. J.; Prokisch, H.; van Meurs, J. B. J.; Melzer, David ( 0000-0002-0170-3838 ) ; Levy, D.
Abstract:
Cigarette smoking is a leading modifiable cause of death worldwide. We hypothesized that cigarette smoking induces extensive transcriptomic changes that lead to target-organ damage and smoking-related diseases. We performed a meta-analysis of transcriptome-wide gene expression using whole blood-derived RNA from 10,233 participants of European ancestry in six cohorts (including 1421 current and 3955 former smokers) to identify associations between smoking and altered gene expression levels. At a false discovery rate (FDR) <0.1, we identified 1270 differentially expressed genes in current vs. never smokers, and 39 genes in former vs. never smokers. Expression levels of 12 genes remained elevated up to 30 years after smoking cessation, suggesting that molecular consequence of smoking may persist for decades. Gene ontology analysis revealed enrichment of smoking-related genes for activation of platelets and lymphocytes, immune response, and apoptosis. Many of the top smoking-related differentially expressed genes, including LRRN3 and GPR15, have DNA methylation loci in promoter regions that were recently reported to be hypomethylated among smokers. By linking differential gene expression with smoking-related disease phenotypes, we demonstrated that stroke and pulmonary function show enrichment for smoking-related gene expression signatures. Mediation analysis revealed expression of several genes (e.g. ALAS2) to be putative mediators of the associations between smoking and inflammatory biomarkers (IL6 and C-reactive protein levels). Our transcriptomic study provides potential insights into the effects of cigarette smoking on gene expression in whole blood and their relations to smoking-related diseases. The results of such analyses may highlight attractive targets for treating or preventing smoking-related health effects.
Citation:
A Whole-Blood Transcriptome Meta-Analysis Identifies Gene Expression Signatures of Cigarette Smoking.2016 Nov 1;25(21):4611-4623 Hum. Mol. Genet.
Publisher:
Oxford Journals
Journal:
Human Molecular Genetics
Issue Date:
29-Aug-2016
URI:
http://hdl.handle.net/11287/619957
DOI:
10.1093/hmg/ddw288
PubMed ID:
28158590
Additional Links:
http://hmg.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=27577875
Type:
Journal Article; Meta-Analysis
Language:
en
ISSN:
1460-2083
Appears in Collections:
Honorary contracts publications; Honorary contracts publications; 2016 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorHuan, T.en
dc.contributor.authorJoehanes, R.en
dc.contributor.authorSchurmann, C.en
dc.contributor.authorSchramm, K.en
dc.contributor.authorPilling, L. C.en
dc.contributor.authorPeters, M. J.en
dc.contributor.authorMägi, R.en
dc.contributor.authorDeMeo, D.en
dc.contributor.authorO'Connor, G. T.en
dc.contributor.authorFerrucci, L.en
dc.contributor.authorTeumer, A.en
dc.contributor.authorHomuth, G.en
dc.contributor.authorBiffar, R.en
dc.contributor.authorVölker, U.en
dc.contributor.authorHerder, C.en
dc.contributor.authorWaldenberger, M.en
dc.contributor.authorPeters, A.en
dc.contributor.authorZeilinger, S.en
dc.contributor.authorMetspalu, A.en
dc.contributor.authorHofman, A.en
dc.contributor.authorUitterlinden, A. G.en
dc.contributor.authorHernandez, D. G.en
dc.contributor.authorSingleton, A. B.en
dc.contributor.authorBandinelli, S.en
dc.contributor.authorMunson, P. J.en
dc.contributor.authorLin, Ho.en
dc.contributor.authorBenjamin, E.J.en
dc.contributor.authorEsko, T.en
dc.contributor.authorGrabe, H. J.en
dc.contributor.authorProkisch, H.en
dc.contributor.authorvan Meurs, J. B. J.en
dc.contributor.authorMelzer, Daviden
dc.contributor.authorLevy, D.en
dc.date.accessioned2016-09-07T09:31:01Z-
dc.date.available2016-09-07T09:31:01Z-
dc.date.issued2016-08-29-
dc.identifier.citationA Whole-Blood Transcriptome Meta-Analysis Identifies Gene Expression Signatures of Cigarette Smoking.2016 Nov 1;25(21):4611-4623 Hum. Mol. Genet.en
dc.identifier.issn1460-2083-
dc.identifier.pmid28158590-
dc.identifier.doi10.1093/hmg/ddw288-
dc.identifier.urihttp://hdl.handle.net/11287/619957-
dc.description.abstractCigarette smoking is a leading modifiable cause of death worldwide. We hypothesized that cigarette smoking induces extensive transcriptomic changes that lead to target-organ damage and smoking-related diseases. We performed a meta-analysis of transcriptome-wide gene expression using whole blood-derived RNA from 10,233 participants of European ancestry in six cohorts (including 1421 current and 3955 former smokers) to identify associations between smoking and altered gene expression levels. At a false discovery rate (FDR) <0.1, we identified 1270 differentially expressed genes in current vs. never smokers, and 39 genes in former vs. never smokers. Expression levels of 12 genes remained elevated up to 30 years after smoking cessation, suggesting that molecular consequence of smoking may persist for decades. Gene ontology analysis revealed enrichment of smoking-related genes for activation of platelets and lymphocytes, immune response, and apoptosis. Many of the top smoking-related differentially expressed genes, including LRRN3 and GPR15, have DNA methylation loci in promoter regions that were recently reported to be hypomethylated among smokers. By linking differential gene expression with smoking-related disease phenotypes, we demonstrated that stroke and pulmonary function show enrichment for smoking-related gene expression signatures. Mediation analysis revealed expression of several genes (e.g. ALAS2) to be putative mediators of the associations between smoking and inflammatory biomarkers (IL6 and C-reactive protein levels). Our transcriptomic study provides potential insights into the effects of cigarette smoking on gene expression in whole blood and their relations to smoking-related diseases. The results of such analyses may highlight attractive targets for treating or preventing smoking-related health effects.en
dc.languageENG-
dc.language.isoenen
dc.publisherOxford Journalsen
dc.relation.urlhttp://hmg.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=27577875en
dc.rightsArchived with thanks to Human molecular geneticsen
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen
dc.titleA Whole-Blood Transcriptome Meta-Analysis Identifies Gene Expression Signatures of Cigarette Smoking.en
dc.typeJournal Articleen
dc.typeMeta-Analysisen
dc.identifier.journalHuman Molecular Geneticsen
dc.type.versionIn press (epub ahead of print)en

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