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.
journal_name
Clin Epigeneticsjournal_title
Clinical epigeneticsauthors
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 Kdoi
10.1186/s13148-018-0558-0subject
Has Abstractpub_date
2018-10-20 00:00:00pages
126issue
1eissn
1868-7075issn
1868-7083pii
10.1186/s13148-018-0558-0journal_volume
10pub_type
杂志文章abstract:BACKGROUND:Prostate cancer (PCa), a highly incident and heterogeneous malignancy, mostly affects men from developed countries. Increased knowledge of the biological mechanisms underlying PCa onset and progression are critical for improved clinical management. MicroRNAs (miRNAs) deregulation is common in human cancers, ...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-015-0076-2
更新日期:2015-04-10 00:00:00
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journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-017-0311-0
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journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-017-0355-1
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journal_title:Clinical epigenetics
pub_type: 杂志文章
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journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-015-0122-0
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journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-020-00930-5
更新日期:2020-09-11 00:00:00
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journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-017-0416-5
更新日期:2017-10-23 00:00:00
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journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-019-0658-5
更新日期:2019-04-27 00:00:00
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journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-016-0220-7
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journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0523-y
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journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-020-00851-3
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abstract:BACKGROUND:Prostate cancer (PC) is a commonly diagnosed malignancy in males, especially in the western hemisphere. The extensive use of multiple biomarkers plays an important role in the diagnosis and prognosis of PC. However, the accuracy of biomarkers for PC prognosis needs to be urgently improved. This study aimed t...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-019-0693-2
更新日期:2019-07-09 00:00:00
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journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-017-0335-5
更新日期:2017-04-14 00:00:00
abstract:BACKGROUND:Epigenetic mechanisms have been suggested to play a role in the development of post-traumatic stress disorder (PTSD). Here, blood-derived DNA methylation data (HumanMethylation450 BeadChip) collected prior to and following combat exposure in three cohorts of male military members were analyzed to assess whet...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-019-0798-7
更新日期:2020-01-13 00:00:00
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journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-017-0432-5
更新日期:2017-12-20 00:00:00
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journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-019-0710-5
更新日期:2019-08-05 00:00:00
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journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-020-00849-x
更新日期:2020-04-21 00:00:00
abstract::In this letter to the editor, we highlight some concerns with a recently published method to estimate gestational age at delivery from DNA methylation data. We conduct novel analyses to highlight the implications of different choices in study design and statistical methods for the prediction of phenotypes from methyla...
journal_title:Clinical epigenetics
pub_type: 信件
doi:10.1186/s13148-017-0402-y
更新日期:2017-09-15 00:00:00
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journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-015-0114-0
更新日期:2015-08-05 00:00:00
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journal_title:Clinical epigenetics
pub_type: 杂志文章
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journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0557-1
更新日期:2018-11-01 00:00:00
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journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0530-z
更新日期:2018-07-18 00:00:00
abstract::Remodeling of the sperm epigenome by lifestyle factors before conception could account for altered metabolism in the next generation offspring. Here, we hypothesized that endurance training changes the epigenome of human spermatozoa. Using small RNA (sRNA) sequencing and reduced representation bisulfite sequencing (RR...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0446-7
更新日期:2018-01-25 00:00:00
abstract::After publication of the original article [1], authors have requested to add a 'J' as middle name for Richard Gilbertson. Hence, full name should be Richard J Gilbertson. ...
journal_title:Clinical epigenetics
pub_type: 已发布勘误
doi:10.1186/s13148-019-0737-7
更新日期:2019-10-21 00:00:00
abstract:BACKGROUND:Frozen-thawed embryo transfer (FET) is increasingly available for the improvement of the success rate of assisted reproductive technologies other than fresh embryo transfer (ET). There have been numerous findings that FET provides better obstetric and perinatal outcomes. However, the birth weight of infants ...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-017-0379-6
更新日期:2017-08-03 00:00:00
abstract:BACKGROUND:Zinc-finger protein 471 (ZNF471) is a member of the Krüppel-associated box domain zinc finger protein (KRAB-ZFP) family. ZNF471 is methylated in squamous cell carcinomas of tongue, stomach and esophageal. However, its role in breast carcinogenesis remains elusive. Here, we studied its expression, functions, ...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-020-00959-6
更新日期:2020-11-17 00:00:00
abstract:BACKGROUND:Preterm birth (PTB), defined as child birth before completion of 37 weeks of gestation, is a major challenge in perinatal health care and can bear long-term medical and financial burden. Over a million children die each year due to PTB complications, and those who survive can face developmental delays. Unfor...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0599-4
更新日期:2019-02-11 00:00:00
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journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-020-00970-x
更新日期:2020-11-23 00:00:00
abstract:BACKGROUND:Recent developments in genomic sequencing have advanced our understanding of the mutations underlying human malignancy. Melanoma is a prototype of an aggressive, genetically heterogeneous cancer notorious for its biologic plasticity and predilection towards developing resistance to targeted therapies. Eviden...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-015-0091-3
更新日期:2015-06-09 00:00:00
abstract::Esophageal cancer is one of the most common malignancies in the world. Squamous cell carcinoma accounts for approximately 90 % of esophageal cancer cases. Genetic and epigenetic changes have been found to accumulate during the development of various cancers, including esophageal squamous carcinoma (ESCC). Tobacco smok...
journal_title:Clinical epigenetics
pub_type: 杂志文章,评审
doi:10.1186/s13148-016-0210-9
更新日期:2016-04-22 00:00:00