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Smoking induces coordinated DNA methylation and gene expression changes in adipose tissue with consequences for metabolic health 06 Biological Sciences 0604 Genetics

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Smoking induces coordinated DNA methylation and gene expression changes in adipose tissue with consequences for metabolic health 06 Biological Sciences 0604 Genetics. / Tsai, Pei Chien; Glastonbury, Craig A.; Eliot, Melissa N.; Bollepalli, Sailalitha; Yet, Idil; Castillo-Fernandez, Juan E.; Carnero-Montoro, Elena; Hardiman, Thomas; Martin, Tiphaine C.; Vickers, Alice; Mangino, Massimo; Ward, Kirsten; Pietiläinen, Kirsi H.; Deloukas, Panos; Spector, Tim D.; Viñuela, Ana; Loucks, Eric B.; Ollikainen, Miina; Kelsey, Karl T.; Small, Kerrin S.; Bell, Jordana T.

In: Clinical Epigenetics, Vol. 10, No. 1, 126, 20.10.2018.

Research output: Contribution to journalArticle

Harvard

Tsai, PC, Glastonbury, CA, Eliot, MN, Bollepalli, S, Yet, I, Castillo-Fernandez, JE, Carnero-Montoro, E, Hardiman, T, Martin, TC, Vickers, A, Mangino, M, Ward, K, Pietiläinen, KH, Deloukas, P, Spector, TD, Viñuela, A, Loucks, EB, Ollikainen, M, Kelsey, KT, Small, KS & Bell, JT 2018, 'Smoking induces coordinated DNA methylation and gene expression changes in adipose tissue with consequences for metabolic health 06 Biological Sciences 0604 Genetics', Clinical Epigenetics, vol. 10, no. 1, 126. https://doi.org/10.1186/s13148-018-0558-0

APA

Tsai, P. C., Glastonbury, C. A., Eliot, M. N., Bollepalli, S., Yet, I., Castillo-Fernandez, J. E., ... Bell, J. T. (2018). Smoking induces coordinated DNA methylation and gene expression changes in adipose tissue with consequences for metabolic health 06 Biological Sciences 0604 Genetics. Clinical Epigenetics, 10(1), [126]. https://doi.org/10.1186/s13148-018-0558-0

Vancouver

Tsai PC, Glastonbury CA, Eliot MN, Bollepalli S, Yet I, Castillo-Fernandez JE et al. Smoking induces coordinated DNA methylation and gene expression changes in adipose tissue with consequences for metabolic health 06 Biological Sciences 0604 Genetics. Clinical Epigenetics. 2018 Oct 20;10(1). 126. https://doi.org/10.1186/s13148-018-0558-0

Author

Tsai, Pei Chien ; Glastonbury, Craig A. ; Eliot, Melissa N. ; Bollepalli, Sailalitha ; Yet, Idil ; Castillo-Fernandez, Juan E. ; Carnero-Montoro, Elena ; Hardiman, Thomas ; Martin, Tiphaine C. ; Vickers, Alice ; Mangino, Massimo ; Ward, Kirsten ; Pietiläinen, Kirsi H. ; Deloukas, Panos ; Spector, Tim D. ; Viñuela, Ana ; Loucks, Eric B. ; Ollikainen, Miina ; Kelsey, Karl T. ; Small, Kerrin S. ; Bell, Jordana T. / Smoking induces coordinated DNA methylation and gene expression changes in adipose tissue with consequences for metabolic health 06 Biological Sciences 0604 Genetics. In: Clinical Epigenetics. 2018 ; Vol. 10, No. 1.

Bibtex Download

@article{2650ce53d2c84a92bd3352ed93a46a6f,
title = "Smoking induces coordinated DNA methylation and gene expression changes in adipose tissue with consequences for metabolic health 06 Biological Sciences 0604 Genetics",
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.",
keywords = "Adipose tissue, DNA methylation, Gene expression, RNA-sequencing, Smoking",
author = "Tsai, {Pei Chien} and Glastonbury, {Craig A.} and Eliot, {Melissa N.} and Sailalitha Bollepalli and Idil Yet and Castillo-Fernandez, {Juan E.} and Elena Carnero-Montoro and Thomas Hardiman and Martin, {Tiphaine C.} and Alice Vickers and Massimo Mangino and Kirsten Ward and Pietil{\"a}inen, {Kirsi H.} and Panos Deloukas and Spector, {Tim D.} and Ana Vi{\~n}uela and Loucks, {Eric B.} and Miina Ollikainen and Kelsey, {Karl T.} and Small, {Kerrin S.} and Bell, {Jordana T.}",
year = "2018",
month = "10",
day = "20",
doi = "10.1186/s13148-018-0558-0",
language = "English",
volume = "10",
journal = "Clinical Epigenetics",
issn = "1868-7075",
publisher = "Springer Verlag",
number = "1",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Smoking induces coordinated DNA methylation and gene expression changes in adipose tissue with consequences for metabolic health 06 Biological Sciences 0604 Genetics

AU - Tsai, Pei Chien

AU - Glastonbury, Craig A.

AU - Eliot, Melissa N.

AU - Bollepalli, Sailalitha

AU - Yet, Idil

AU - Castillo-Fernandez, Juan E.

AU - Carnero-Montoro, Elena

AU - Hardiman, Thomas

AU - Martin, Tiphaine C.

AU - Vickers, Alice

AU - Mangino, Massimo

AU - Ward, Kirsten

AU - Pietiläinen, Kirsi H.

AU - Deloukas, Panos

AU - Spector, Tim D.

AU - Viñuela, Ana

AU - Loucks, Eric B.

AU - Ollikainen, Miina

AU - Kelsey, Karl T.

AU - Small, Kerrin S.

AU - Bell, Jordana T.

PY - 2018/10/20

Y1 - 2018/10/20

N2 - 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.

AB - 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.

KW - Adipose tissue

KW - DNA methylation

KW - Gene expression

KW - RNA-sequencing

KW - Smoking

UR - http://www.scopus.com/inward/record.url?scp=85055077729&partnerID=8YFLogxK

U2 - 10.1186/s13148-018-0558-0

DO - 10.1186/s13148-018-0558-0

M3 - Article

C2 - 30342560

AN - SCOPUS:85055077729

VL - 10

JO - Clinical Epigenetics

JF - Clinical Epigenetics

SN - 1868-7075

IS - 1

M1 - 126

ER -

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