Smoking induces coordinated DNA methylation and gene expression changes in adipose tissue with consequences for metabolic health

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Tsai , P-C , Glastonbury , C A , Eliot , M N , Bollepalli , S , Yet , I , Castillo-Fernandez , J E , Carnero-Montoro , E , Hardiman , T , Martin , T C , Vickers , A , Mangino , M , Ward , K , Pietilaeinen , K H , Deloukas , P , Spector , T D , Vinuela , A , Loucks , E B , Ollikainen , M , Kelsey , K T , Small , K S & Bell , J T 2018 , ' Smoking induces coordinated DNA methylation and gene expression changes in adipose tissue with consequences for metabolic health ' , Clinical epigenetics , vol. 10 , 126 .

Title: Smoking induces coordinated DNA methylation and gene expression changes in adipose tissue with consequences for metabolic health
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; Pietilaeinen, Kirsi H.; Deloukas, Panos; Spector, Tim D.; Vinuela, Ana; Loucks, Eric B.; Ollikainen, Miina; Kelsey, Karl T.; Small, Kerrin S.; Bell, Jordana T.
Contributor organization: Institute for Molecular Medicine Finland
Department of Public Health
University of Helsinki
HUS Abdominal Center
Epigenetics of Complex Diseases and Traits
Date: 2018-10-20
Language: eng
Number of pages: 21
Belongs to series: Clinical epigenetics
ISSN: 1868-7083
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 arid 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.
Subject: Smoking
DNA methylation
Gene expression
Adipose tissue
3122 Cancers
3142 Public health care science, environmental and occupational health
3111 Biomedicine
Peer reviewed: Yes
Usage restriction: openAccess
Self-archived version: publishedVersion

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