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An epigenome-wide study of body mass index and DNA methylation in blood using participants from the Sister Study cohort
Umeå University, Faculty of Medicine, Department of Radiation Sciences. Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA.ORCID iD: 0000-0001-8540-6891
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2017 (English)In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 41, no 1, 194-199 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND/OBJECTIVES: The relationship between obesity and chronic disease risk is well-established; the underlying biological mechanisms driving this risk increase may include obesity-related epigenetic modifications. To explore this hypothesis, we conducted a genome-wide analysis of DNA methylation and body mass index (BMI) using data from a subset of women in the Sister Study.

SUBJECTS/METHODS: The Sister Study is a cohort of 50 884 US women who had a sister with breast cancer but were free of breast cancer themselves at enrollment. Study participants completed examinations which included measurements of height and weight, and provided blood samples. Blood DNA methylation data generated with the Illumina Infinium HumanMethylation27 BeadChip array covering 27,589 CpG sites was available for 871 women from a prior study of breast cancer and DNA methylation. To identify differentially methylated CpG sites associated with BMI, we analyzed this methylation data using robust linear regression with adjustment for age and case status. For those CpGs passing the false discovery rate significance level, we examined the association in a replication set comprised of a non-overlapping group of 187 women from the Sister Study who had DNA methylation data generated using the Infinium HumanMethylation450 BeadChip array. Analysis of this expanded 450 K array identified additional BMI-associated sites which were investigated with targeted pyrosequencing.

RESULTS: Four CpG sites reached genome-wide significance (false discovery rate (FDR) q<0.05) in the discovery set and associations for all four were significant at strict Bonferroni correction in the replication set. An additional 23 sites passed FDR in the replication set and five were replicated by pyrosequencing in the discovery set. Several of the genes identified including ANGPT4, RORC, SOCS3, FSD2, XYLT1, ABCG1, STK39, ASB2 and CRHR2 have been linked to obesity and obesity-related chronic diseases.

CONCLUSIONS: Our findings support the hypothesis that obesity-related epigenetic differences are detectable in blood and may be related to risk of chronic disease.

Place, publisher, year, edition, pages
2017. Vol. 41, no 1, 194-199 p.
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:umu:diva-132605DOI: 10.1038/ijo.2016.184ISI: 000394143100026PubMedID: 27773939OAI: oai:DiVA.org:umu-132605DiVA: diva2:1082762
Available from: 2017-03-17 Created: 2017-03-17 Last updated: 2017-04-04Bibliographically approved

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CiteExportLink to record
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Citation style
  • apa
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