Roby Joehanes, Allan C Just, Riccardo E Marioni, Luke C Pilling, Lindsay M Reynolds, Pooja R Mandaviya, Weihua Guan, Tao Xu, Cathy E Elks, Stella Aslibekyan, Hortensia Moreno-Macias, Jennifer A Smith, Jennifer A Brody, Radhika Dhingra, Paul Yousefi, James S Pankow, Sonja Kunze, Sonia H Shah, Allan F McRae, Kurt Lohman, Jin Sha, Devin M Absher, Luigi Ferrucci, Wei Zhao, Ellen W Demerath, Jan Bressler, Megan L Grove, Tianxiao Huan, Chunyu Liu, Michael M Mendelson, Chen Yao, Douglas P Kiel, Annette Peters, Rui Wang-Sattler, Peter M Visscher, Naomi R Wray, John M Starr, Jingzhong Ding, Carlos J Rodriguez, Nicholas J Wareham, Marguerite R Irvin, Degui Zhi, Myrto Barrdahl, Paolo Vineis, Srikant Ambatipudi, André G Uitterlinden, Albert Hofman, Joel Schwartz, Elena Colicino, Lifang Hou, Pantel S Vokonas, Dena G Hernandez, Andrew B Singleton, Stefania Bandinelli, Stephen T Turner, Erin B Ware, Alicia K Smith, Torsten Klengel, Elisabeth B Binder, Bruce M Psaty, Kent D Taylor, Sina A Gharib, Brenton R Swenson, Liming Liang, Dawn L DeMeo, George T O'Connor, Zdenko Herceg, Kerry J Ressler, Karen N Conneely, Nona Sotoodehnia, Sharon L R Kardia, David Melzer, Andrea A Baccarelli, Joyce B J van Meurs, Isabelle Romieu, Donna K Arnett, Ken K Ong, Yongmei Liu, Melanie Waldenberger, Ian J Deary, Myriam Fornage, Daniel Levy, Stephanie J London
{"title":"吸烟的表观遗传学特征","authors":"Roby Joehanes, Allan C Just, Riccardo E Marioni, Luke C Pilling, Lindsay M Reynolds, Pooja R Mandaviya, Weihua Guan, Tao Xu, Cathy E Elks, Stella Aslibekyan, Hortensia Moreno-Macias, Jennifer A Smith, Jennifer A Brody, Radhika Dhingra, Paul Yousefi, James S Pankow, Sonja Kunze, Sonia H Shah, Allan F McRae, Kurt Lohman, Jin Sha, Devin M Absher, Luigi Ferrucci, Wei Zhao, Ellen W Demerath, Jan Bressler, Megan L Grove, Tianxiao Huan, Chunyu Liu, Michael M Mendelson, Chen Yao, Douglas P Kiel, Annette Peters, Rui Wang-Sattler, Peter M Visscher, Naomi R Wray, John M Starr, Jingzhong Ding, Carlos J Rodriguez, Nicholas J Wareham, Marguerite R Irvin, Degui Zhi, Myrto Barrdahl, Paolo Vineis, Srikant Ambatipudi, André G Uitterlinden, Albert Hofman, Joel Schwartz, Elena Colicino, Lifang Hou, Pantel S Vokonas, Dena G Hernandez, Andrew B Singleton, Stefania Bandinelli, Stephen T Turner, Erin B Ware, Alicia K Smith, Torsten Klengel, Elisabeth B Binder, Bruce M Psaty, Kent D Taylor, Sina A Gharib, Brenton R Swenson, Liming Liang, Dawn L DeMeo, George T O'Connor, Zdenko Herceg, Kerry J Ressler, Karen N Conneely, Nona Sotoodehnia, Sharon L R Kardia, David Melzer, Andrea A Baccarelli, Joyce B J van Meurs, Isabelle Romieu, Donna K Arnett, Ken K Ong, Yongmei Liu, Melanie Waldenberger, Ian J Deary, Myriam Fornage, Daniel Levy, Stephanie J London","doi":"10.1161/CIRCGENETICS.116.001506","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>DNA methylation leaves a long-term signature of smoking exposure and is one potential mechanism by which tobacco exposure predisposes to adverse health outcomes, such as cancers, osteoporosis, lung, and cardiovascular disorders.</p><p><strong>Methods and results: </strong>To comprehensively determine the association between cigarette smoking and DNA methylation, we conducted a meta-analysis of genome-wide DNA methylation assessed using the Illumina BeadChip 450K array on 15 907 blood-derived DNA samples from participants in 16 cohorts (including 2433 current, 6518 former, and 6956 never smokers). Comparing current versus never smokers, 2623 cytosine-phosphate-guanine sites (CpGs), annotated to 1405 genes, were statistically significantly differentially methylated at Bonferroni threshold of P<1×10<sup>-7</sup> (18 760 CpGs at false discovery rate <0.05). Genes annotated to these CpGs were enriched for associations with several smoking-related traits in genome-wide studies including pulmonary function, cancers, inflammatory diseases, and heart disease. Comparing former versus never smokers, 185 of the CpGs that differed between current and never smokers were significant P<1×10<sup>-7</sup> (2623 CpGs at false discovery rate <0.05), indicating a pattern of persistent altered methylation, with attenuation, after smoking cessation. Transcriptomic integration identified effects on gene expression at many differentially methylated CpGs.</p><p><strong>Conclusions: </strong>Cigarette smoking has a broad impact on genome-wide methylation that, at many loci, persists many years after smoking cessation. Many of the differentially methylated genes were novel genes with respect to biological effects of smoking and might represent therapeutic targets for prevention or treatment of tobacco-related diseases. Methylation at these sites could also serve as sensitive and stable biomarkers of lifetime exposure to tobacco smoke.</p>","PeriodicalId":48940,"journal":{"name":"Circulation-Cardiovascular Genetics","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2016-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5267325/pdf/","citationCount":"0","resultStr":"{\"title\":\"Epigenetic Signatures of Cigarette Smoking.\",\"authors\":\"Roby Joehanes, Allan C Just, Riccardo E Marioni, Luke C Pilling, Lindsay M Reynolds, Pooja R Mandaviya, Weihua Guan, Tao Xu, Cathy E Elks, Stella Aslibekyan, Hortensia Moreno-Macias, Jennifer A Smith, Jennifer A Brody, Radhika Dhingra, Paul Yousefi, James S Pankow, Sonja Kunze, Sonia H Shah, Allan F McRae, Kurt Lohman, Jin Sha, Devin M Absher, Luigi Ferrucci, Wei Zhao, Ellen W Demerath, Jan Bressler, Megan L Grove, Tianxiao Huan, Chunyu Liu, Michael M Mendelson, Chen Yao, Douglas P Kiel, Annette Peters, Rui Wang-Sattler, Peter M Visscher, Naomi R Wray, John M Starr, Jingzhong Ding, Carlos J Rodriguez, Nicholas J Wareham, Marguerite R Irvin, Degui Zhi, Myrto Barrdahl, Paolo Vineis, Srikant Ambatipudi, André G Uitterlinden, Albert Hofman, Joel Schwartz, Elena Colicino, Lifang Hou, Pantel S Vokonas, Dena G Hernandez, Andrew B Singleton, Stefania Bandinelli, Stephen T Turner, Erin B Ware, Alicia K Smith, Torsten Klengel, Elisabeth B Binder, Bruce M Psaty, Kent D Taylor, Sina A Gharib, Brenton R Swenson, Liming Liang, Dawn L DeMeo, George T O'Connor, Zdenko Herceg, Kerry J Ressler, Karen N Conneely, Nona Sotoodehnia, Sharon L R Kardia, David Melzer, Andrea A Baccarelli, Joyce B J van Meurs, Isabelle Romieu, Donna K Arnett, Ken K Ong, Yongmei Liu, Melanie Waldenberger, Ian J Deary, Myriam Fornage, Daniel Levy, Stephanie J London\",\"doi\":\"10.1161/CIRCGENETICS.116.001506\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>DNA methylation leaves a long-term signature of smoking exposure and is one potential mechanism by which tobacco exposure predisposes to adverse health outcomes, such as cancers, osteoporosis, lung, and cardiovascular disorders.</p><p><strong>Methods and results: </strong>To comprehensively determine the association between cigarette smoking and DNA methylation, we conducted a meta-analysis of genome-wide DNA methylation assessed using the Illumina BeadChip 450K array on 15 907 blood-derived DNA samples from participants in 16 cohorts (including 2433 current, 6518 former, and 6956 never smokers). Comparing current versus never smokers, 2623 cytosine-phosphate-guanine sites (CpGs), annotated to 1405 genes, were statistically significantly differentially methylated at Bonferroni threshold of P<1×10<sup>-7</sup> (18 760 CpGs at false discovery rate <0.05). Genes annotated to these CpGs were enriched for associations with several smoking-related traits in genome-wide studies including pulmonary function, cancers, inflammatory diseases, and heart disease. Comparing former versus never smokers, 185 of the CpGs that differed between current and never smokers were significant P<1×10<sup>-7</sup> (2623 CpGs at false discovery rate <0.05), indicating a pattern of persistent altered methylation, with attenuation, after smoking cessation. Transcriptomic integration identified effects on gene expression at many differentially methylated CpGs.</p><p><strong>Conclusions: </strong>Cigarette smoking has a broad impact on genome-wide methylation that, at many loci, persists many years after smoking cessation. Many of the differentially methylated genes were novel genes with respect to biological effects of smoking and might represent therapeutic targets for prevention or treatment of tobacco-related diseases. Methylation at these sites could also serve as sensitive and stable biomarkers of lifetime exposure to tobacco smoke.</p>\",\"PeriodicalId\":48940,\"journal\":{\"name\":\"Circulation-Cardiovascular Genetics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2016-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5267325/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Circulation-Cardiovascular Genetics\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1161/CIRCGENETICS.116.001506\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2016/9/20 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Circulation-Cardiovascular Genetics","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1161/CIRCGENETICS.116.001506","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2016/9/20 0:00:00","PubModel":"Epub","JCR":"Q","JCRName":"Medicine","Score":null,"Total":0}
Background: DNA methylation leaves a long-term signature of smoking exposure and is one potential mechanism by which tobacco exposure predisposes to adverse health outcomes, such as cancers, osteoporosis, lung, and cardiovascular disorders.
Methods and results: To comprehensively determine the association between cigarette smoking and DNA methylation, we conducted a meta-analysis of genome-wide DNA methylation assessed using the Illumina BeadChip 450K array on 15 907 blood-derived DNA samples from participants in 16 cohorts (including 2433 current, 6518 former, and 6956 never smokers). Comparing current versus never smokers, 2623 cytosine-phosphate-guanine sites (CpGs), annotated to 1405 genes, were statistically significantly differentially methylated at Bonferroni threshold of P<1×10-7 (18 760 CpGs at false discovery rate <0.05). Genes annotated to these CpGs were enriched for associations with several smoking-related traits in genome-wide studies including pulmonary function, cancers, inflammatory diseases, and heart disease. Comparing former versus never smokers, 185 of the CpGs that differed between current and never smokers were significant P<1×10-7 (2623 CpGs at false discovery rate <0.05), indicating a pattern of persistent altered methylation, with attenuation, after smoking cessation. Transcriptomic integration identified effects on gene expression at many differentially methylated CpGs.
Conclusions: Cigarette smoking has a broad impact on genome-wide methylation that, at many loci, persists many years after smoking cessation. Many of the differentially methylated genes were novel genes with respect to biological effects of smoking and might represent therapeutic targets for prevention or treatment of tobacco-related diseases. Methylation at these sites could also serve as sensitive and stable biomarkers of lifetime exposure to tobacco smoke.
期刊介绍：
Circulation: Genomic and Precision Medicine considers all types of original research articles, including studies conducted in human subjects, laboratory animals, in vitro, and in silico. Articles may include investigations of: clinical genetics as applied to the diagnosis and management of monogenic or oligogenic cardiovascular disorders; the molecular basis of complex cardiovascular disorders, including genome-wide association studies, exome and genome sequencing-based association studies, coding variant association studies, genetic linkage studies, epigenomics, transcriptomics, proteomics, metabolomics, and metagenomics; integration of electronic health record data or patient-generated data with any of the aforementioned approaches, including phenome-wide association studies, or with environmental or lifestyle factors; pharmacogenomics; regulation of gene expression; gene therapy and therapeutic genomic editing; systems biology approaches to the diagnosis and management of cardiovascular disorders; novel methods to perform any of the aforementioned studies; and novel applications of precision medicine. Above all, we seek studies with relevance to human cardiovascular biology and disease. Manuscripts are examined by the editorial staff and usually evaluated by expert reviewers assigned by the editors. Both clinical and basic articles will also be subject to statistical review, when appropriate. Provisional or final acceptance is based on originality, scientific content, and topical balance of the journal. Decisions are communicated by email, generally within six weeks. The editors will not discuss a decision about a manuscript over the phone. All rebuttals must be submitted in writing to the editorial office.
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