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Genetics and Epigenetics

An epigenome-wide study of body mass index and DNA methylation in blood using participants from the Sister Study cohort

International Journal of Obesity volume 41, pages 194–199 (2017)Cite this article

Subjects

Abstract

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.

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Acknowledgements

We thank Dr Sarah Reese and Dr Yong-Moon Park for their critical review of this manuscript. We would also like to thank the women who volunteered to participate in the Sister Study. We thank the National Institutes of Health (NIH) Center for Inherited Disease Research and the National Institute of Environmental Health Sciences (NIEHS) Molecular Genetics Core and Microarray Core for their technical support. This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01 ES044005, Z01 ES044032, and Z01 ES049033) which provided funding for design and conduct of the study; collection, management, analysis and interpretation of the data; and preparation, review and approval of the manuscript.

Author contributions

All authors contributed to the design of the study, the generation, analysis, and interpretation of results, and the drafting and revision of the manuscript. All authors have reviewed and approved the final manuscript. LEW and JAT confirm they had full access to the data and final responsibility for the decision to submit for publication.

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Authors and Affiliations

  1. Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA

    L E Wilson, S Harlid, Z Xu, D P Sandler & J A Taylor

  2. Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden

    S Harlid

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  1. L E Wilson
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Correspondence to J A Taylor.

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Wilson, L., Harlid, S., Xu, Z. et al. An epigenome-wide study of body mass index and DNA methylation in blood using participants from the Sister Study cohort. Int J Obes 41, 194–199 (2017). https://doi.org/10.1038/ijo.2016.184

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