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Genome-wide analysis reveals DNA methylation markers that vary with both age and obesity
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
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2014 (English)In: Gene, ISSN 0378-1119, E-ISSN 1879-0038, Vol. 548, no 1, 61-67 p.Article in journal (Refereed) Published
Abstract [en]

The combination of the obesity epidemic and an aging population presents growing challenges for the healthcare system. Obesity and aging are major risk factors for a diverse number of diseases and it is of importance to understand their interaction and the underlying molecular mechanisms. Herein the authors examined the methylation levels of 27578 CpG sites in 46 samples from adult peripheral blood. The effect of obesity and aging was ascertained with general linear models. More than one hundred probes were correlated to aging, nine of which belonged to the KEGG group map04080. Additionally, 10 CpG sites had diverse methylation profiles in obese and lean individuals, one of which was the telomerase catalytic subunit (TERT). In eight of ten cases the methylation change was reverted between obese and lean individuals. One region proved to be differentially methylated with obesity (LINC00304) independent of age. This study provides evidence that obesity influences age driven epigenetic changes, which provides a molecular link between aging and obesity. This link and the identified markers may prove to be valuable biomarkers for the understanding of the molecular basis of aging, obesity and associated diseases.

Place, publisher, year, edition, pages
2014. Vol. 548, no 1, 61-67 p.
Keyword [en]
Epigenetics, Microarray, Aging, Obesity
National Category
Medical Genetics
Identifiers
URN: urn:nbn:se:uu:diva-230920DOI: 10.1016/j.gene.2014.07.009ISI: 000340329100010OAI: oai:DiVA.org:uu-230920DiVA: diva2:743599
Available from: 2014-09-04 Created: 2014-09-01 Last updated: 2017-12-05Bibliographically approved
In thesis
1. Genome wide methylation analysis and obesity related traits
Open this publication in new window or tab >>Genome wide methylation analysis and obesity related traits
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The most studied form of epigenetics is DNA methylation and several studies have investigated the link between the methylome and body weight. In paper I we analyzed the methylation profile of whole blood in 46 subjects measured with Illumina 27K chip. We provide evidence that obesity influences age driven epigenetic changes. These identified markers may prove to be valuable biomarkers for the understanding of the molecular basis of aging, obesity and associated diseases. In paper II we studied the effect of bariatric surgery, and subsequent weight loss, on methylation and relating this to normal weight controls. In paper II we found 115 promoters had altered methylation after surgery. Among these promoters, an enrichment for genes involved in metabolic processes was found (n=36, p<0.05). In addition, these 51 promoters was more similar after surgery to that of normal-weight controls, than it had been at baseline (p<0.0001). One of the major comorbidities of severe obesity is obstructive sleep apnea and lack of sleep is highly correlated with obesity. Paper III shows how acute sleep deprivation increases portion size and affects food choice in 16 young men. In paper VI, whole genome DNA methylation profiles of whole blood was assessed following both conditions by the Illumina 450K methylation in the same trial as in paper III. This paper shows how sleep deprivation affects DNA methylation profiles of whole blood in a manner both dependent and independent on monocyte subpopulations. Hypothesis free genome wide analysis revealed differential methylation in ING5, a gene previously known to be differentially expressed in sleep deprivation. 

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2015. 40 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1101
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-248685 (URN)978-91-554-9236-6 (ISBN)
Public defence
2015-06-05, BMC C2:301, Husargatan 3, Uppsala, 13:00 (English)
Opponent
Supervisors
Available from: 2015-05-12 Created: 2015-04-07 Last updated: 2015-07-07Bibliographically approved

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Almén, Markus SällmanNilsson, Emil K.Fredriksson, RobertSchiöth, Helgi B.

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