A Whole-Blood Transcriptome Meta-Analysis Identifies Gene Expression Signatures of Cigarette Smoking
Year: 2016
Type: review
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 the 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 the 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.
Source: Human Molecular Genetics
DOI: 10.1093/hmg/ddw288
Authors: Tianxiao Huan, Roby Joehanes, Claudia Schurmann, Katharina Schramm, Luke C. Pilling, Marjolein J. Peters, Reedik Mägi, Dawn DeMeo, George T O'Connor, Luigi Ferrucci, Alexander Teumer, Georg Homuth, Reiner Biffar, Uwe Völker, Christian Herder, Melanie Waldenberger, Annette Peters, Sonja Zeilinger, Andres Metspalu, Albert Hofman, André G. Uitterlinden, Dena G. Hernandez, Andrew B. Singleton, Stefania Bandinelli, Peter J. Munson, Honghuang Lin, Emelia J. Benjamin, Tõnu Esko, Hans J. Grabe, Holger Prokisch, Joyce B.J. van Meurs, David Melzer, Daniel Levy
Institutions: Boston University, National Heart, Lung, and Blood Institute, Framingham Heart Study, National Heart, Lung, and Blood Institute Division of Intramural Research, Harvard University, Hebrew SeniorLife, Universitätsmedizin Greifswald, Icahn School of Medicine at Mount Sinai, Helmholtz Munich, Institut für Humangenetik, Technical University of Munich, University of Exeter, Erasmus MC, Netherlands Consortium for Healthy Ageing, University of Tartu, National Institute on Aging, Universität Greifswald, Deutsches Diabetes-Zentrum e.V., German Center for Diabetes Research, Heinrich Heine University Düsseldorf, National Institutes of Health, Azienda Sanitaria di Firenze, Center for Information Technology, Broad Institute, Boston Children's Hospital, German Center for Neurodegenerative Diseases
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,390
Funders: U.S. Department of Health and Human Services, ZonMw, Erasmus Medisch Centrum, Ministero della Salute, National Institutes of Health, European Regional Development Fund, National Institute on Aging, National Heart, Lung, and Blood Institute, Center for Information Technology, National Institute on Minority Health and Health Disparities, NHLBI Division of Intramural Research
Awards: G1035741774, G1248102086, G1789381357, American Heart Association Tobacco Regulation and Addiction Center (A-TRAC), G2495888254, G250621538, G278200998, G2857511458, G3205625555, G3362311673, G3405256882, Vasoactive Peptides that Stimulate Smooth Muscles, G374919288, G3819938352, G4122201895, G4507648799, Aging and Inflammation: Longitudinal Markers and Genetics in the Framingham Study, G4652745033, INFLAMMATION: CORRELATES AND PROGNOSIS IN FRAMINGHAM, Framingham: Inflammation, Genes & Cardiovascular Disease, The Framingham Heart Study, G7333524540, G8683204365, HISPANIC SECONDARY STROKE PREVENTION INITIATIVE, G8962124162, G9000124674
OpenAlex ID: W2513841576