A genome-wide methylation study on obesity: Differential variability and differential methylation

Besides differential methylation, DNA methylation variation has recently been proposed and demonstrated to be a potential contributing factor to cancer risk. Here we aim to examine whether differential variability in methylation is also an important feature of obesity, a typical non-malignant common...

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Main Authors:	Xu, Xiaojing, Su, Shaoyong, Barnes, Vernon A., De Miguel, Carmen, Pollock, Jennifer, Ownby, Dennis, Shi, Huidong, Zhu, Haidong, Snieder, Harold, Wang, Xiaoling
Format:	Online
Language:	English
Published:	Landes Bioscience 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3741222/

id	pubmed-3741222
recordtype	oai_dc
spelling	pubmed-37412222013-08-28 A genome-wide methylation study on obesity: Differential variability and differential methylation Xu, Xiaojing Su, Shaoyong Barnes, Vernon A. De Miguel, Carmen Pollock, Jennifer Ownby, Dennis Shi, Huidong Zhu, Haidong Snieder, Harold Wang, Xiaoling Research Paper Besides differential methylation, DNA methylation variation has recently been proposed and demonstrated to be a potential contributing factor to cancer risk. Here we aim to examine whether differential variability in methylation is also an important feature of obesity, a typical non-malignant common complex disease. We analyzed genome-wide methylation profiles of over 470,000 CpGs in peripheral blood samples from 48 obese and 48 lean African-American youth aged 14–20 y old. A substantial number of differentially variable CpG sites (DVCs), using statistics based on variances, as well as a substantial number of differentially methylated CpG sites (DMCs), using statistics based on means, were identified. Similar to the findings in cancers, DVCs generally exhibited an outlier structure and were more variable in cases than in controls. By randomly splitting the current sample into a discovery and validation set, we observed that both the DVCs and DMCs identified from the first set could independently predict obesity status in the second set. Furthermore, both the genes harboring DMCs and the genes harboring DVCs showed significant enrichment of genes identified by genome-wide association studies on obesity and related diseases, such as hypertension, dyslipidemia, type 2 diabetes and certain types of cancers, supporting their roles in the etiology and pathogenesis of obesity. We generalized the recent finding on methylation variability in cancer research to obesity and demonstrated that differential variability is also an important feature of obesity-related methylation changes. Future studies on the epigenetics of obesity will benefit from both statistics based on means and statistics based on variances. Landes Bioscience 2013-05-01 2013-04-17 /pmc/articles/PMC3741222/ /pubmed/23644594 http://dx.doi.org/10.4161/epi.24506 Text en Copyright © 2013 Landes Bioscience http://creativecommons.org/licenses/by-nc/3.0/ This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Xu, Xiaojing Su, Shaoyong Barnes, Vernon A. De Miguel, Carmen Pollock, Jennifer Ownby, Dennis Shi, Huidong Zhu, Haidong Snieder, Harold Wang, Xiaoling
spellingShingle	Xu, Xiaojing Su, Shaoyong Barnes, Vernon A. De Miguel, Carmen Pollock, Jennifer Ownby, Dennis Shi, Huidong Zhu, Haidong Snieder, Harold Wang, Xiaoling A genome-wide methylation study on obesity: Differential variability and differential methylation
author_facet	Xu, Xiaojing Su, Shaoyong Barnes, Vernon A. De Miguel, Carmen Pollock, Jennifer Ownby, Dennis Shi, Huidong Zhu, Haidong Snieder, Harold Wang, Xiaoling
author_sort	Xu, Xiaojing
title	A genome-wide methylation study on obesity: Differential variability and differential methylation
title_short	A genome-wide methylation study on obesity: Differential variability and differential methylation
title_full	A genome-wide methylation study on obesity: Differential variability and differential methylation
title_fullStr	A genome-wide methylation study on obesity: Differential variability and differential methylation
title_full_unstemmed	A genome-wide methylation study on obesity: Differential variability and differential methylation
title_sort	genome-wide methylation study on obesity: differential variability and differential methylation
description	Besides differential methylation, DNA methylation variation has recently been proposed and demonstrated to be a potential contributing factor to cancer risk. Here we aim to examine whether differential variability in methylation is also an important feature of obesity, a typical non-malignant common complex disease. We analyzed genome-wide methylation profiles of over 470,000 CpGs in peripheral blood samples from 48 obese and 48 lean African-American youth aged 14–20 y old. A substantial number of differentially variable CpG sites (DVCs), using statistics based on variances, as well as a substantial number of differentially methylated CpG sites (DMCs), using statistics based on means, were identified. Similar to the findings in cancers, DVCs generally exhibited an outlier structure and were more variable in cases than in controls. By randomly splitting the current sample into a discovery and validation set, we observed that both the DVCs and DMCs identified from the first set could independently predict obesity status in the second set. Furthermore, both the genes harboring DMCs and the genes harboring DVCs showed significant enrichment of genes identified by genome-wide association studies on obesity and related diseases, such as hypertension, dyslipidemia, type 2 diabetes and certain types of cancers, supporting their roles in the etiology and pathogenesis of obesity. We generalized the recent finding on methylation variability in cancer research to obesity and demonstrated that differential variability is also an important feature of obesity-related methylation changes. Future studies on the epigenetics of obesity will benefit from both statistics based on means and statistics based on variances.
publisher	Landes Bioscience
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3741222/
_version_	1612002445663141888

A genome-wide methylation study on obesity: Differential variability and differential methylation

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