title: Genome-Wide Methylation Analysis Identifies Specific Epigenetic Marks In Severely Obese Children.
abstract: Obesity is a heterogeneous disease with many different subtypes. Epigenetics could contribute to these differences. The aim of this study was to investigate genome-wide DNA methylation searching for methylation marks associated with obesity in children and adolescents. We studied DNA methylation profiles in whole blood cells from 40 obese children and controls using Illumina Infinium HumanMethylation450 BeadChips. After correction for cell heterogeneity and multiple tests, we found that compared to lean controls, 31 CpGs are differentially methylated in obese patients. A greatest proportion of these CpGs is hypermethylated in obesity and located in CpG shores regions. We next focused on severely obese children and identified 151 differentially methylated CpGs among which 10 with a difference in methylation greater than 10%. The top pathways enriched among the identified CpGs included the "IRS1 target genes" and several pathways in cancer diseases. This study represents the first effort to search for differences in methylation in obesity and severe obesity, which may help understanding these different forms of obesity and their complications.
authors.affiliation: INSERM U1169, Bicêtre Hospital, Paris Sud University, Le Kremlin-Bicêtre, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Fradin
authors.affiliation: Pierre et Marie Curie University, INSERM, Paris, U707, France.
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Boëlle
authors.affiliation: INSERM U1169, Bicêtre Hospital, Paris Sud University, Le Kremlin-Bicêtre, France.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Belot
authors.affiliation: INSERM U1169, Bicêtre Hospital, Paris Sud University, Le Kremlin-Bicêtre, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Lachaux
authors.affiliation: Laboratory for Epigenetics and Environment, Centre National de Génotypage, CEA - Institut de Génomique, Evry, France.
authors.forename: Jorg
authors.initials: J
authors.lastname: Tost
authors.affiliation: Centre National de Génotypage, CEA - Institut de Génomique, Evry, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Besse
authors.affiliation: Centre National de Génotypage, CEA - Institut de Génomique, Evry, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Deleuze
authors.affiliation: Department of Pediatric Endocrinology, Bicêtre Hospital, Paris Sud University, Le Kremlin-Bicêtre, France.
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: De Filippo
authors.affiliation: INSERM U1169, Bicêtre Hospital, Paris Sud University, Le Kremlin-Bicêtre, France.|Department of Pediatric Endocrinology, Bicêtre Hospital, Paris Sud University, Le Kremlin-Bicêtre, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Bougnères
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D015894:Genome, Human; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics; D008297:Male; D009767:Obesity, Morbid / Q000235:genetics*
chemical_list: C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins