Interindividual Variation in DNA Methylation at a Putative POMC Metastable Epiallele Is Associated with Obesity.


Kühnen, P; Handke, D; Waterland, RA; Hennig, BJ; Silver, M; Fulford, AJ; Dominguez-Salas, P; Moore, SE; Prentice, AM; Spranger, J; Hinney, A; Hebebrand, J; Heppner, FL; Walzer, L; Grötzinger, C; Gromoll, J; Wiegand, S; Grüters, A; Krude, H; (2016) Interindividual Variation in DNA Methylation at a Putative POMC Metastable Epiallele Is Associated with Obesity. Cell metabolism, 24 (3). pp. 502-9. ISSN 1550-4131 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.<br/>

Item Type: Article
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Population Health (2012- ) > Dept of Nutrition and Public Health Interventions Research (2003-2012)
Faculty of Epidemiology and Population Health > Dept of Population Health (2012- )
PubMed ID: 27568547
Web of Science ID: 384016500021
URI: http://researchonline.lshtm.ac.uk/id/eprint/2868360

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