Interindividual variation in DNA methylation at a putative POMC metastable epiallele is associated with obesity
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 heritabilit...
| Autores principales: | , , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | Journal Article |
| Lenguaje: | Inglés |
| Publicado: |
Elsevier
2016
|
| Materias: | |
| Acceso en línea: | https://hdl.handle.net/10568/77018 |
| _version_ | 1855527233899200512 |
|---|---|
| author | Kühnen, P. Handke, D. Waterland, R.A. Hennig, B.J. Silver, M. Fulford, A.J. Domínguez Salas, Paula Moore, S.E. Prentice, A.M. Spranger, J. Hinney, A. Hebebrand, J. Heppner, F.L. Walzer, L. Grötzinger, C. Gromoll, J. Wiegand, S. Grüters, A. Krude, H. |
| author_browse | Domínguez Salas, Paula Fulford, A.J. Gromoll, J. Grötzinger, C. Grüters, A. Handke, D. Hebebrand, J. Hennig, B.J. Heppner, F.L. Hinney, A. Krude, H. Kühnen, P. Moore, S.E. Prentice, A.M. Silver, M. Spranger, J. Walzer, L. Waterland, R.A. Wiegand, S. |
| author_facet | Kühnen, P. Handke, D. Waterland, R.A. Hennig, B.J. Silver, M. Fulford, A.J. Domínguez Salas, Paula Moore, S.E. Prentice, A.M. Spranger, J. Hinney, A. Hebebrand, J. Heppner, F.L. Walzer, L. Grötzinger, C. Gromoll, J. Wiegand, S. Grüters, A. Krude, H. |
| author_sort | Kühnen, P. |
| collection | Repository of Agricultural Research Outputs (CGSpace) |
| description | 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. |
| format | Journal Article |
| id | CGSpace77018 |
| institution | CGIAR Consortium |
| language | Inglés |
| publishDate | 2016 |
| publishDateRange | 2016 |
| publishDateSort | 2016 |
| publisher | Elsevier |
| publisherStr | Elsevier |
| record_format | dspace |
| spelling | CGSpace770182024-08-29T11:41:31Z Interindividual variation in DNA methylation at a putative POMC metastable epiallele is associated with obesity Kühnen, P. Handke, D. Waterland, R.A. Hennig, B.J. Silver, M. Fulford, A.J. Domínguez Salas, Paula Moore, S.E. Prentice, A.M. Spranger, J. Hinney, A. Hebebrand, J. Heppner, F.L. Walzer, L. Grötzinger, C. Gromoll, J. Wiegand, S. Grüters, A. Krude, H. health 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. 2016-09 2016-09-09T13:26:55Z 2016-09-09T13:26:55Z Journal Article https://hdl.handle.net/10568/77018 en Limited Access Elsevier Kühnen, P., Handke, D., Waterland, R.A., Hennig, B.J., Silver, M., Fulford, A.J., Dominguez-Salas, P., Moore, S.E., Prentice, A.M., Spranger, J., Hinney, A., Hebebrand, J., Heppner, F.L., Walzer, L., Grötzinger, C., Gromoll, J., Wiegand, S., Grüters, A. and Krude, H. 2016. Interindividual variation in DNA methylation at a putative POMC metastable epiallele is associated with obesity. Cell Metabolism 24(3): 502–509. |
| spellingShingle | health Kühnen, P. Handke, D. Waterland, R.A. Hennig, B.J. Silver, M. Fulford, A.J. Domínguez Salas, Paula Moore, S.E. Prentice, A.M. Spranger, J. Hinney, A. Hebebrand, J. Heppner, F.L. Walzer, L. Grötzinger, C. Gromoll, J. Wiegand, S. Grüters, A. Krude, H. Interindividual variation in DNA methylation at a putative POMC metastable epiallele is associated with obesity |
| title | Interindividual variation in DNA methylation at a putative POMC metastable epiallele is associated with obesity |
| title_full | Interindividual variation in DNA methylation at a putative POMC metastable epiallele is associated with obesity |
| title_fullStr | Interindividual variation in DNA methylation at a putative POMC metastable epiallele is associated with obesity |
| title_full_unstemmed | Interindividual variation in DNA methylation at a putative POMC metastable epiallele is associated with obesity |
| title_short | Interindividual variation in DNA methylation at a putative POMC metastable epiallele is associated with obesity |
| title_sort | interindividual variation in dna methylation at a putative pomc metastable epiallele is associated with obesity |
| topic | health |
| url | https://hdl.handle.net/10568/77018 |
| work_keys_str_mv | AT kuhnenp interindividualvariationindnamethylationataputativepomcmetastableepialleleisassociatedwithobesity AT handked interindividualvariationindnamethylationataputativepomcmetastableepialleleisassociatedwithobesity AT waterlandra interindividualvariationindnamethylationataputativepomcmetastableepialleleisassociatedwithobesity AT hennigbj interindividualvariationindnamethylationataputativepomcmetastableepialleleisassociatedwithobesity AT silverm interindividualvariationindnamethylationataputativepomcmetastableepialleleisassociatedwithobesity AT fulfordaj interindividualvariationindnamethylationataputativepomcmetastableepialleleisassociatedwithobesity AT dominguezsalaspaula interindividualvariationindnamethylationataputativepomcmetastableepialleleisassociatedwithobesity AT moorese interindividualvariationindnamethylationataputativepomcmetastableepialleleisassociatedwithobesity AT prenticeam interindividualvariationindnamethylationataputativepomcmetastableepialleleisassociatedwithobesity AT sprangerj interindividualvariationindnamethylationataputativepomcmetastableepialleleisassociatedwithobesity AT hinneya interindividualvariationindnamethylationataputativepomcmetastableepialleleisassociatedwithobesity AT hebebrandj interindividualvariationindnamethylationataputativepomcmetastableepialleleisassociatedwithobesity AT heppnerfl interindividualvariationindnamethylationataputativepomcmetastableepialleleisassociatedwithobesity AT walzerl interindividualvariationindnamethylationataputativepomcmetastableepialleleisassociatedwithobesity AT grotzingerc interindividualvariationindnamethylationataputativepomcmetastableepialleleisassociatedwithobesity AT gromollj interindividualvariationindnamethylationataputativepomcmetastableepialleleisassociatedwithobesity AT wiegands interindividualvariationindnamethylationataputativepomcmetastableepialleleisassociatedwithobesity AT grutersa interindividualvariationindnamethylationataputativepomcmetastableepialleleisassociatedwithobesity AT krudeh interindividualvariationindnamethylationataputativepomcmetastableepialleleisassociatedwithobesity |