Smoking induces coordinated DNA methylation and gene expression changes in adipose tissue with consequences for metabolic health
Abstract Background Tobacco smoking is a risk factor for multiple diseases, including cardiovascular disease and diabetes. Many smoking-associated signals have been detected in the blood methylome, but the extent to which these changes are widespread to metabolically relevant tissues, and impact gen...
Main Authors: | , , , , , , , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2018-10-01
|
Series: | Clinical Epigenetics |
Subjects: | |
Online Access: | http://link.springer.com/article/10.1186/s13148-018-0558-0 |
id |
doaj-3bba2d6c73104eca9851fbbee9580cd6 |
---|---|
record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Pei-Chien Tsai Craig A. Glastonbury Melissa N. Eliot Sailalitha Bollepalli Idil Yet Juan E. Castillo-Fernandez Elena Carnero-Montoro Thomas Hardiman Tiphaine C. Martin Alice Vickers Massimo Mangino Kirsten Ward Kirsi H. Pietiläinen Panos Deloukas Tim D. Spector Ana Viñuela Eric B. Loucks Miina Ollikainen Karl T. Kelsey Kerrin S. Small Jordana T. Bell |
spellingShingle |
Pei-Chien Tsai Craig A. Glastonbury Melissa N. Eliot Sailalitha Bollepalli Idil Yet Juan E. Castillo-Fernandez Elena Carnero-Montoro Thomas Hardiman Tiphaine C. Martin Alice Vickers Massimo Mangino Kirsten Ward Kirsi H. Pietiläinen Panos Deloukas Tim D. Spector Ana Viñuela Eric B. Loucks Miina Ollikainen Karl T. Kelsey Kerrin S. Small Jordana T. Bell Smoking induces coordinated DNA methylation and gene expression changes in adipose tissue with consequences for metabolic health Clinical Epigenetics Smoking DNA methylation Gene expression RNA-sequencing Adipose tissue |
author_facet |
Pei-Chien Tsai Craig A. Glastonbury Melissa N. Eliot Sailalitha Bollepalli Idil Yet Juan E. Castillo-Fernandez Elena Carnero-Montoro Thomas Hardiman Tiphaine C. Martin Alice Vickers Massimo Mangino Kirsten Ward Kirsi H. Pietiläinen Panos Deloukas Tim D. Spector Ana Viñuela Eric B. Loucks Miina Ollikainen Karl T. Kelsey Kerrin S. Small Jordana T. Bell |
author_sort |
Pei-Chien Tsai |
title |
Smoking induces coordinated DNA methylation and gene expression changes in adipose tissue with consequences for metabolic health |
title_short |
Smoking induces coordinated DNA methylation and gene expression changes in adipose tissue with consequences for metabolic health |
title_full |
Smoking induces coordinated DNA methylation and gene expression changes in adipose tissue with consequences for metabolic health |
title_fullStr |
Smoking induces coordinated DNA methylation and gene expression changes in adipose tissue with consequences for metabolic health |
title_full_unstemmed |
Smoking induces coordinated DNA methylation and gene expression changes in adipose tissue with consequences for metabolic health |
title_sort |
smoking induces coordinated dna methylation and gene expression changes in adipose tissue with consequences for metabolic health |
publisher |
BMC |
series |
Clinical Epigenetics |
issn |
1868-7075 1868-7083 |
publishDate |
2018-10-01 |
description |
Abstract Background Tobacco smoking is a risk factor for multiple diseases, including cardiovascular disease and diabetes. Many smoking-associated signals have been detected in the blood methylome, but the extent to which these changes are widespread to metabolically relevant tissues, and impact gene expression or metabolic health, remains unclear. Methods We investigated smoking-associated DNA methylation and gene expression variation in adipose tissue biopsies from 542 healthy female twins. Replication, tissue specificity, and longitudinal stability of the smoking-associated effects were explored in additional adipose, blood, skin, and lung samples. We characterized the impact of adipose tissue smoking methylation and expression signals on metabolic disease risk phenotypes, including visceral fat. Results We identified 42 smoking-methylation and 42 smoking-expression signals, where five genes (AHRR, CYP1A1, CYP1B1, CYTL1, F2RL3) were both hypo-methylated and upregulated in current smokers. CYP1A1 gene expression achieved 95% prediction performance of current smoking status. We validated and replicated a proportion of the signals in additional primary tissue samples, identifying tissue-shared effects. Smoking leaves systemic imprints on DNA methylation after smoking cessation, with stronger but shorter-lived effects on gene expression. Metabolic disease risk traits such as visceral fat and android-to-gynoid ratio showed association with methylation at smoking markers with functional impacts on expression, such as CYP1A1, and at tissue-shared smoking signals, such as NOTCH1. At smoking-signals, BHLHE40 and AHRR DNA methylation and gene expression levels in current smokers were predictive of future gain in visceral fat upon smoking cessation. Conclusions Our results provide the first comprehensive characterization of coordinated DNA methylation and gene expression markers of smoking in adipose tissue. The findings relate to human metabolic health and give insights into understanding the widespread health consequence of smoking outside of the lung. |
topic |
Smoking DNA methylation Gene expression RNA-sequencing Adipose tissue |
url |
http://link.springer.com/article/10.1186/s13148-018-0558-0 |
work_keys_str_mv |
AT peichientsai smokinginducescoordinateddnamethylationandgeneexpressionchangesinadiposetissuewithconsequencesformetabolichealth AT craigaglastonbury smokinginducescoordinateddnamethylationandgeneexpressionchangesinadiposetissuewithconsequencesformetabolichealth AT melissaneliot smokinginducescoordinateddnamethylationandgeneexpressionchangesinadiposetissuewithconsequencesformetabolichealth AT sailalithabollepalli smokinginducescoordinateddnamethylationandgeneexpressionchangesinadiposetissuewithconsequencesformetabolichealth AT idilyet smokinginducescoordinateddnamethylationandgeneexpressionchangesinadiposetissuewithconsequencesformetabolichealth AT juanecastillofernandez smokinginducescoordinateddnamethylationandgeneexpressionchangesinadiposetissuewithconsequencesformetabolichealth AT elenacarneromontoro smokinginducescoordinateddnamethylationandgeneexpressionchangesinadiposetissuewithconsequencesformetabolichealth AT thomashardiman smokinginducescoordinateddnamethylationandgeneexpressionchangesinadiposetissuewithconsequencesformetabolichealth AT tiphainecmartin smokinginducescoordinateddnamethylationandgeneexpressionchangesinadiposetissuewithconsequencesformetabolichealth AT alicevickers smokinginducescoordinateddnamethylationandgeneexpressionchangesinadiposetissuewithconsequencesformetabolichealth AT massimomangino smokinginducescoordinateddnamethylationandgeneexpressionchangesinadiposetissuewithconsequencesformetabolichealth AT kirstenward smokinginducescoordinateddnamethylationandgeneexpressionchangesinadiposetissuewithconsequencesformetabolichealth AT kirsihpietilainen smokinginducescoordinateddnamethylationandgeneexpressionchangesinadiposetissuewithconsequencesformetabolichealth AT panosdeloukas smokinginducescoordinateddnamethylationandgeneexpressionchangesinadiposetissuewithconsequencesformetabolichealth AT timdspector smokinginducescoordinateddnamethylationandgeneexpressionchangesinadiposetissuewithconsequencesformetabolichealth AT anavinuela smokinginducescoordinateddnamethylationandgeneexpressionchangesinadiposetissuewithconsequencesformetabolichealth AT ericbloucks smokinginducescoordinateddnamethylationandgeneexpressionchangesinadiposetissuewithconsequencesformetabolichealth AT miinaollikainen smokinginducescoordinateddnamethylationandgeneexpressionchangesinadiposetissuewithconsequencesformetabolichealth AT karltkelsey smokinginducescoordinateddnamethylationandgeneexpressionchangesinadiposetissuewithconsequencesformetabolichealth AT kerrinssmall smokinginducescoordinateddnamethylationandgeneexpressionchangesinadiposetissuewithconsequencesformetabolichealth AT jordanatbell smokinginducescoordinateddnamethylationandgeneexpressionchangesinadiposetissuewithconsequencesformetabolichealth |
_version_ |
1725282156496814080 |
spelling |
doaj-3bba2d6c73104eca9851fbbee9580cd62020-11-25T00:42:29ZengBMCClinical Epigenetics1868-70751868-70832018-10-0110112110.1186/s13148-018-0558-0Smoking induces coordinated DNA methylation and gene expression changes in adipose tissue with consequences for metabolic healthPei-Chien Tsai0Craig A. Glastonbury1Melissa N. Eliot2Sailalitha Bollepalli3Idil Yet4Juan E. Castillo-Fernandez5Elena Carnero-Montoro6Thomas Hardiman7Tiphaine C. Martin8Alice Vickers9Massimo Mangino10Kirsten Ward11Kirsi H. Pietiläinen12Panos Deloukas13Tim D. Spector14Ana Viñuela15Eric B. Loucks16Miina Ollikainen17Karl T. Kelsey18Kerrin S. Small19Jordana T. Bell20Department of Twin Research and Genetic Epidemiology, King’s College LondonDepartment of Twin Research and Genetic Epidemiology, King’s College LondonDepartment of Epidemiology, Brown University School of Public HealthInstitute for Molecular Medicine Finland (FIMM) and Department of Public Health, University of HelsinkiDepartment of Twin Research and Genetic Epidemiology, King’s College LondonDepartment of Twin Research and Genetic Epidemiology, King’s College LondonDepartment of Twin Research and Genetic Epidemiology, King’s College LondonDepartment of Twin Research and Genetic Epidemiology, King’s College LondonDepartment of Twin Research and Genetic Epidemiology, King’s College LondonDepartment of Twin Research and Genetic Epidemiology, King’s College LondonDepartment of Twin Research and Genetic Epidemiology, King’s College LondonDepartment of Twin Research and Genetic Epidemiology, King’s College LondonResearch Programs Unit, Diabetes and Obesity, Obesity Research Unit, University of HelsinkiWilliam Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of LondonDepartment of Twin Research and Genetic Epidemiology, King’s College LondonDepartment of Twin Research and Genetic Epidemiology, King’s College LondonDepartment of Epidemiology, Brown University School of Public HealthInstitute for Molecular Medicine Finland (FIMM) and Department of Public Health, University of HelsinkiDepartment of Epidemiology, Brown University School of Public HealthDepartment of Twin Research and Genetic Epidemiology, King’s College LondonDepartment of Twin Research and Genetic Epidemiology, King’s College LondonAbstract Background Tobacco smoking is a risk factor for multiple diseases, including cardiovascular disease and diabetes. Many smoking-associated signals have been detected in the blood methylome, but the extent to which these changes are widespread to metabolically relevant tissues, and impact gene expression or metabolic health, remains unclear. Methods We investigated smoking-associated DNA methylation and gene expression variation in adipose tissue biopsies from 542 healthy female twins. Replication, tissue specificity, and longitudinal stability of the smoking-associated effects were explored in additional adipose, blood, skin, and lung samples. We characterized the impact of adipose tissue smoking methylation and expression signals on metabolic disease risk phenotypes, including visceral fat. Results We identified 42 smoking-methylation and 42 smoking-expression signals, where five genes (AHRR, CYP1A1, CYP1B1, CYTL1, F2RL3) were both hypo-methylated and upregulated in current smokers. CYP1A1 gene expression achieved 95% prediction performance of current smoking status. We validated and replicated a proportion of the signals in additional primary tissue samples, identifying tissue-shared effects. Smoking leaves systemic imprints on DNA methylation after smoking cessation, with stronger but shorter-lived effects on gene expression. Metabolic disease risk traits such as visceral fat and android-to-gynoid ratio showed association with methylation at smoking markers with functional impacts on expression, such as CYP1A1, and at tissue-shared smoking signals, such as NOTCH1. At smoking-signals, BHLHE40 and AHRR DNA methylation and gene expression levels in current smokers were predictive of future gain in visceral fat upon smoking cessation. Conclusions Our results provide the first comprehensive characterization of coordinated DNA methylation and gene expression markers of smoking in adipose tissue. The findings relate to human metabolic health and give insights into understanding the widespread health consequence of smoking outside of the lung.http://link.springer.com/article/10.1186/s13148-018-0558-0SmokingDNA methylationGene expressionRNA-sequencingAdipose tissue |