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|Εξειδίκευση τύπου : ||Άρθρο σε επιστημονικό περιοδικό|
|Τίτλος: ||Epigenome-wide association study of adiposity and future risk of obesity-related diseases|
|Δημιουργός/Συγγραφέας: ||Campanella G.|
de Kok T.M.C.M.
[EL] Γεωργιάδης, Παναγιώτης[EN] Georgiadis, Panagiotis
[EL] Κυρτόπουλος, Σωτήριος Α.[EN] Kyrtopoulos, Soterios A.
|Εκδότης: ||Nature Publishing Group|
|Άλλο: ||PubMed ID: 29713043|
|Περίληψη: ||Background: Obesity is an established risk factor for several common chronic diseases such as breast and colorectal cancer, metabolic and cardiovascular diseases; however, the biological basis for these relationships is not fully understood. To explore the association of obesity with these conditions, we investigated peripheral blood leucocyte (PBL) DNA methylation markers for adiposity and their contribution to risk of incident breast and colorectal cancer and myocardial infarction. Methods: DNA methylation profiles (Illumina Infinium® HumanMethylation450 BeadChip) from 1941 individuals from four population-based European cohorts were analysed in relation to body mass index, waist circumference, waist-hip and waist-height ratio within a meta-analytical framework. In a subset of these individuals, data on genome-wide gene expression level, biomarkers of glucose and lipid metabolism were also available. Validation of methylation markers associated with all adiposity measures was performed in 358 individuals. Finally, we investigated the association of obesity-related methylation marks with breast, colorectal cancer and myocardial infarction within relevant subsets of the discovery population. Results: We identified 40 CpG loci with methylation levels associated with at least one adiposity measure. Of these, one CpG locus (cg06500161) in ABCG1 was associated with all four adiposity measures (P = 9.07×10− 8 to 3.27×10−18) and lower transcriptional activity of the full-length isoform of ABCG1 (P = 6.00×10−7), higher triglyceride levels (P = 5.37×10− 9) and higher triglycerides-to-HDL cholesterol ratio (P = 1.03×10−10). Of the 40 informative and obesity-related CpG loci, two (in IL2RB and FGF18) were significantly associated with colorectal cancer (inversely, P < 1.6×10−3) and one intergenic locus on chromosome 1 was inversely associated with myocardial infarction (P < 1.25×10−3), independently of obesity and established risk factors. Conclusion: Our results suggest that epigenetic changes, in particular altered DNA methylation patterns, may be an intermediate biomarker at the intersection of obesity and obesity-related diseases, and could offer clues as to underlying biological mechanisms.|
|Τίτλος πηγής δημοσίευσης: ||International Journal of Obesity|
|Θεματική Κατηγορία: ||[EL] Χημεία (Γενικά)[EN] Chemistry (General)|
[EL] Γενετική[EN] Genetics
|Αξιολόγηση από ομότιμους (peer reviewed): ||Ναι|
|Κάτοχος πνευματικών δικαιωμάτων: ||© 2018, Macmillan Publishers Limited, part of Springer Nature.|
|Όροι και προϋποθέσεις δικαιωμάτων: ||All Open Access, Green|
|Σημειώσεις: ||232997; Ecumenical Project for International Cooperation; Health Research; Compagnia di San Paolo; Medical Research Council, MRC: MR/L01341X/1; Engineering and Physical Sciences Research Council; National Institute for Health Research; World Cancer Research Fund; Imperial College London; Imperial College Healthcare NHS Trust; European Commission: 226756; European Research Council; Ministerie van Volksgezondheid, Welzijn en Sport; Human Genetics Foundation-Torino, HuGeF-Torino; Associazione Italiana per la Ricerca sul Cancro.|
Funding EPIC-Italy was financially supported by the Italian Association for Cancer Research (AIRC). Genome-wide DNA methylation profiling and bisulphite pyrosequencing of EPIC-Italy samples was financially supported by the Human Genetics Foundation (HuGeF) and Compagnia di San Paolo. The EnviroGenoMarkers project was financially supported by the European Union (grant agreement 226756 to Soterios A. Kyrtopoulos). EPIC-Netherlands was financially supported by the Dutch Ministry of Public Health, Welfare, and Sports (VWS), by the Netherlands Cancer Registry, by LK Research Funds, by Dutch Prevention Funds, by the Netherlands Organisation for Health Research and Development (ZON), and by the World Cancer Research Fund (WCRF). Genome-wide DNA methylation profiling of EPIC-Netherlands samples was financially supported by internal Imperial College funds. Genome-wide DNA methylation and gene expression profiling of NOWAC samples was financially supported by the European Research Council for frontier research, Advanced Grant TICE—Transcriptomics in Cancer Epidemiology (number 232997, period 2009–2014).
|Εμφανίζεται στις συλλογές:||Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο|
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