| Autor: |
Liam McAllan, Damir Baranasic, Sergio Villicaña, Scarlett Brown, Weihua Zhang, Benjamin Lehne, Marco Adamo, Andrew Jenkinson, Mohamed Elkalaawy, Borzoueh Mohammadi, Majid Hashemi, Nadia Fernandes, Nathalie Lambie, Richard Williams, Colette Christiansen, Youwen Yang, Liudmila Zudina, Vasiliki Lagou, Sili Tan, Juan Castillo-Fernandez, James W. D. King, Richie Soong, Paul Elliott, James Scott, Inga Prokopenko, Inês Cebola, Marie Loh, Boris Lenhard, Rachel L. Batterham, Jordana T. Bell, John C. Chambers, Jaspal S. Kooner, William R. Scott |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Nature Communications, Vol 14, Iss 1, Pp 1-20 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2041-1723 |
| DOI: |
10.1038/s41467-023-38439-z |
| Popis: |
Abstract DNA methylation variations are prevalent in human obesity but evidence of a causative role in disease pathogenesis is limited. Here, we combine epigenome-wide association and integrative genomics to investigate the impact of adipocyte DNA methylation variations in human obesity. We discover extensive DNA methylation changes that are robustly associated with obesity (N = 190 samples, 691 loci in subcutaneous and 173 loci in visceral adipocytes, P 500 target genes, and identify putative methylation-transcription factor interactions. Through Mendelian Randomisation, we infer causal effects of methylation on obesity and obesity-induced metabolic disturbances at 59 independent loci. Targeted methylation sequencing, CRISPR-activation and gene silencing in adipocytes, further identifies regional methylation variations, underlying regulatory elements and novel cellular metabolic effects. Our results indicate DNA methylation is an important determinant of human obesity and its metabolic complications, and reveal mechanisms through which altered methylation may impact adipocyte functions. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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Full text from SpringerLink