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Interindividual variation in DNA methylation at a putative POMC metastable epiallele Is associated with obesity

Interindividual variation in DNA methylation at a putative POMC metastable epiallele Is associated with obesity

Kühnen, Peter, Handke, Daniela, Waterland, Robert A., Hennig, Branwen J., Silver, Matt, Fulford, Anthony J., Dominguez-Salas, Paula ORCID: 0000-0001-8753-4221, Moore, Sophie E., Prentice, Andrew M., Spranger, Joachim, Hinney, Anke, Hebebrand, Johannes, Heppner, Frank L., Walzer, Lena, Grötzinger, Carsten, Gromoll, Jörg, Wiegand, Susanna, Grüters, Annette and Krude, Heiko (2016) Interindividual variation in DNA methylation at a putative POMC metastable epiallele Is associated with obesity. Cell Metabolism, 24 (3). pp. 502-509. ISSN 1550-4131 (Print), 1932-7420 (Online) (doi:https://doi.org/10.1016/j.cmet.2016.08.001)

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Abstract

The estimated heritability of human BMI is close to 75%, but identified genetic variants explain only a small fraction of interindividual body-weight variation. Inherited epigenetic variants identified in mouse models named “metastable epialleles” could in principle explain this “missing heritability.” We provide evidence that methylation in a variably methylated region (VMR) in the pro-opiomelanocortin gene (POMC), particularly in postmortem human laser-microdissected melanocyte-stimulating hormone (MSH)-positive neurons, is strongly associated with individual BMI. Using cohorts from different ethnic backgrounds, including a Gambian cohort, we found evidence suggesting that methylation of the POMC VMR is established in the early embryo and that offspring methylation correlates with the paternal somatic methylation pattern. Furthermore, it is associated with levels of maternal one-carbon metabolites at conception and stable during postnatal life. Together, these data suggest that the POMC VMR may be a human metastable epiallele that influences body-weight regulation.

Item Type: Article
Faculty / Department / Research Group: Faculty of Engineering & Science
Faculty of Engineering & Science > Natural Resources Institute
Faculty of Engineering & Science > Natural Resources Institute > Food & Markets Department
Last Modified: 28 Jul 2020 15:51
Selected for GREAT 2016: None
Selected for GREAT 2017: None
Selected for GREAT 2018: None
Selected for GREAT 2019: None
Selected for REF2021: None
URI: http://gala.gre.ac.uk/id/eprint/28965

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