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Open AccessArticle

Methylome-Wide Association Study in Peripheral White Blood Cells Focusing on Central Obesity and Inflammation

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Department of Nutrition, Food Sciences and Physiology, University of Navarra, Irunlarrea 1,31008 Pamplona, Spain
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Centre for Nutrition Research, University of Navarra, Irunlarrea 1, 31008, Pamplona, Spain
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Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, 28029, Madrid, Spain
4
Navarra Institute for Health Research (IdiSNa), 31008, Pamplona, Spain
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Department of Bioinformatics, Making Genetics S.L., 31002, Pamplona, Spain
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Precision Nutrition and Cardiometabolic Health Program, Madrid Institute for Advanced Studies (IMDEA), IMDEA Food, 28049, Madrid, Spain
*
Author to whom correspondence should be addressed.
Genes 2019, 10(6), 444; https://doi.org/10.3390/genes10060444
Received: 17 April 2019 / Revised: 3 June 2019 / Accepted: 7 June 2019 / Published: 11 June 2019
(This article belongs to the Special Issue DNA Methylation in Health and Diseases)
Epigenetic signatures such as DNA methylation may be associated with specific obesity traits in different tissues. The onset and development of some obesity-related complications are often linked to visceral fat accumulation. The aim of this study was to explore DNA methylation levels in peripheral white blood cells to identify epigenetic methylation marks associated with waist circumference (WC). DNA methylation levels were assessed using Infinium Human Methylation 450K and MethylationEPIC beadchip (Illumina) to search for putative associations with WC values of 473 participants from the Methyl Epigenome Network Association (MENA) project. Statistical analysis and Ingenuity Pathway Analysis (IPA) were employed for assessing the relationship between methylation and WC. A total of 669 CpGs were statistically associated with WC (FDR < 0.05, slope ≥ |0.1|). From these CpGs, 375 CpGs evidenced a differential methylation pattern between females with WC ≤ 88 and > 88 cm, and 95 CpGs between males with WC ≤ 102 and > 102 cm. These differentially methylated CpGs are located in genes related to inflammation and obesity according to IPA. Receiver operating characteristic (ROC) curves of the top four significant differentially methylated CpGs separated by sex discriminated individuals with presence or absence of abdominal fat. ROC curves of all the CpGs from females and one CpG from males were validated in an independent sample (n = 161). These methylation results add further insights about the relationships between obesity, adiposity-associated comorbidities, and DNA methylation where inflammation processes may be involved. View Full-Text
Keywords: waist circumference; epigenetics; DNA methylation waist circumference; epigenetics; DNA methylation
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Arpón, A.; Milagro, F.I.; Ramos-Lopez, O.; Mansego, M.L.; Riezu-Boj, J.-I.; Martínez, J.A., on Behalf of the MENA Project; Methylome-Wide Association Study in Peripheral White Blood Cells Focusing on Central Obesity and Inflammation. Genes 2019, 10, 444.

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