Epigenome-wide methylation differences in a group of lean and obese women – A HUNT Study

Abstract Knowledge of epigenetically regulated biomarkers linked to obesity development is still scarce. Improving molecular understanding of the involved factors and pathways would improve obesity phenotype characterization and reveal potentially relevant targets for obesity intervention. The Illum...

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Autores principales: Kirsti Kvaløy, Christian Magnus Page, Turid Lingaas Holmen
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Publicado: Nature Portfolio 2018
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spelling oai:doaj.org-article:10b4271b851f45b8ad0dc658aa1e06e72021-12-02T15:07:45ZEpigenome-wide methylation differences in a group of lean and obese women – A HUNT Study10.1038/s41598-018-34003-82045-2322https://doaj.org/article/10b4271b851f45b8ad0dc658aa1e06e72018-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-34003-8https://doaj.org/toc/2045-2322Abstract Knowledge of epigenetically regulated biomarkers linked to obesity development is still scarce. Improving molecular understanding of the involved factors and pathways would improve obesity phenotype characterization and reveal potentially relevant targets for obesity intervention. The Illumina Infinium HumanMethylation450 BeadChip was used in a leucocyte epigenome-wide association study (EWAS) to quantify differential DNA methylation in 60 lean compared with 60 obese young women. Replication was done in monozygotic twins discordant for obesity. At adolescence and adulthood, the two weight groups differed significantly in obesity-related traits and metabolic risk factors. Differential hypomethylation was overrepresented in obese compared to lean women. In the adjusted model, the EWAS revealed 10 differentially methylated CpG sites linked to 8 gene loci – COX6A1P2/FGD2, SBNO2, TEX41, RPS6KA2, IGHE/IGHG1/IGHD, DMAP1, SOCS3, and SETBP1– and an enhancer locus at chromosome 2 (2p25.1). The sites linked to TEX41, IGHE/IGHG1/IGHD, DMAP1, and SETBP1 were novel findings, while COX6A1P/FGD2, SBNO2, RPS6KA2, and SOCS3 had been identified previously with concordant direction of effects. RPS6KA2, DMAP1, and SETBP1 were replicated in the BMI-discordant monozygotic twin cohort using the FDR of 5%.Kirsti KvaløyChristian Magnus PageTurid Lingaas HolmenNature PortfolioarticleDifferentially Methylated SitesEpigenome-wide Association Studies (EWAS)Obesity DevelopmentTest Construction (TEX41)Obesity SusceptibilityMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-9 (2018)
institution DOAJ
collection DOAJ
language EN
topic Differentially Methylated Sites
Epigenome-wide Association Studies (EWAS)
Obesity Development
Test Construction (TEX41)
Obesity Susceptibility
Medicine
R
Science
Q
spellingShingle Differentially Methylated Sites
Epigenome-wide Association Studies (EWAS)
Obesity Development
Test Construction (TEX41)
Obesity Susceptibility
Medicine
R
Science
Q
Kirsti Kvaløy
Christian Magnus Page
Turid Lingaas Holmen
Epigenome-wide methylation differences in a group of lean and obese women – A HUNT Study
description Abstract Knowledge of epigenetically regulated biomarkers linked to obesity development is still scarce. Improving molecular understanding of the involved factors and pathways would improve obesity phenotype characterization and reveal potentially relevant targets for obesity intervention. The Illumina Infinium HumanMethylation450 BeadChip was used in a leucocyte epigenome-wide association study (EWAS) to quantify differential DNA methylation in 60 lean compared with 60 obese young women. Replication was done in monozygotic twins discordant for obesity. At adolescence and adulthood, the two weight groups differed significantly in obesity-related traits and metabolic risk factors. Differential hypomethylation was overrepresented in obese compared to lean women. In the adjusted model, the EWAS revealed 10 differentially methylated CpG sites linked to 8 gene loci – COX6A1P2/FGD2, SBNO2, TEX41, RPS6KA2, IGHE/IGHG1/IGHD, DMAP1, SOCS3, and SETBP1– and an enhancer locus at chromosome 2 (2p25.1). The sites linked to TEX41, IGHE/IGHG1/IGHD, DMAP1, and SETBP1 were novel findings, while COX6A1P/FGD2, SBNO2, RPS6KA2, and SOCS3 had been identified previously with concordant direction of effects. RPS6KA2, DMAP1, and SETBP1 were replicated in the BMI-discordant monozygotic twin cohort using the FDR of 5%.
format article
author Kirsti Kvaløy
Christian Magnus Page
Turid Lingaas Holmen
author_facet Kirsti Kvaløy
Christian Magnus Page
Turid Lingaas Holmen
author_sort Kirsti Kvaløy
title Epigenome-wide methylation differences in a group of lean and obese women – A HUNT Study
title_short Epigenome-wide methylation differences in a group of lean and obese women – A HUNT Study
title_full Epigenome-wide methylation differences in a group of lean and obese women – A HUNT Study
title_fullStr Epigenome-wide methylation differences in a group of lean and obese women – A HUNT Study
title_full_unstemmed Epigenome-wide methylation differences in a group of lean and obese women – A HUNT Study
title_sort epigenome-wide methylation differences in a group of lean and obese women – a hunt study
publisher Nature Portfolio
publishDate 2018
url https://doaj.org/article/10b4271b851f45b8ad0dc658aa1e06e7
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AT christianmagnuspage epigenomewidemethylationdifferencesinagroupofleanandobesewomenahuntstudy
AT turidlingaasholmen epigenomewidemethylationdifferencesinagroupofleanandobesewomenahuntstudy
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