| Title: |
Adipose methylome integrative-omic analyses reveal genetic and dietary metabolic health drivers and insulin resistance classifiers |
| Authors: |
Christiansen, C; Tomlinson, M; Eliot, M; Nilsson, E; Costeira, R; Xia, Y; Villicaña, S; Mompeo, O; Wells, P; Castillo-Fernandez, J; Potier, L; Vohl, MC; Tchernof, A; Moustafa, JES; Menni, C; Steves, CJ; Kelsey, K; Ling, C; Grundberg, E; Small, KS; Bell, JT |
| Source: |
Genome Medicine , 14 , Article 75. (2022) |
| Publisher Information: |
Springer Science and Business Media LLC |
| Publication Year: |
2022 |
| Collection: |
University College London: UCL Discovery |
| Subject Terms: |
DNA methylation; Visceral fat; Adiposity; Integrative omics |
| Description: |
Background: There is considerable evidence for the importance of the DNA methylome in metabolic health, for example, a robust methylation signature has been associated with body mass index (BMI). However, visceral fat (VF) mass accumulation is a greater risk factor for metabolic disease than BMI alone. In this study, we dissect the subcutaneous adipose tissue (SAT) methylome signature relevant to metabolic health by focusing on VF as the major risk factor of metabolic disease. We integrate results with genetic, blood methylation, SAT gene expression, blood metabolomic, dietary intake and metabolic phenotype data to assess and quantify genetic and environmental drivers of the identified signals, as well as their potential functional roles. / Methods: Epigenome-wide association analyses were carried out to determine visceral fat mass-associated differentially methylated positions (VF-DMPs) in SAT samples from 538 TwinsUK participants. Validation and replication were performed in 333 individuals from 3 independent cohorts. To assess functional impacts of the VF-DMPs, the association between VF and gene expression was determined at the genes annotated to the VF-DMPs and an association analysis was carried out to determine whether methylation at the VF-DMPs is associated with gene expression. Further epigenetic analyses were carried out to compare methylation levels at the VF-DMPs as the response variables and a range of different metabolic health phenotypes including android:gynoid fat ratio (AGR), lipids, blood metabolomic profiles, insulin resistance, T2D and dietary intake variables. The results from all analyses were integrated to identify signals that exhibit altered SAT function and have strong relevance to metabolic health. / Results: We identified 1181 CpG positions in 788 genes to be differentially methylated with VF (VF-DMPs) with significant enrichment in the insulin signalling pathway. Follow-up cross-omic analysis of VF-DMPs integrating genetics, gene expression, metabolomics, diet, and metabolic traits ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://discovery.ucl.ac.uk/id/eprint/10170129/ |
| Availability: |
https://discovery.ucl.ac.uk/id/eprint/10170129/1/Adipose%20methylome%20integrative-omic%20analyses%20reveal%20genetic%20and%20dietary%20metabolic%20health%20drivers%20and%20insulin%20resistance%20class.pdf; https://discovery.ucl.ac.uk/id/eprint/10170129/ |
| Rights: |
open |
| Accession Number: |
edsbas.6D89080F |
| Database: |
BASE |