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@article{McAllan:2023:10.1038/s41467-023-38439-z,
author = {McAllan, L and Baranasic, D and Villicaña, S and Brown, S and Zhang, W and Lehne, B and Adamo, M and Jenkinson, A and Elkalaawy, M and Mohammadi, B and Hashemi, M and Fernandes, N and Lambie, N and Williams, R and Christiansen, C and Yang, Y and Zudina, L and Lagou, V and Tan, S and Castillo-Fernandez, J and King, JWD and Soong, R and Elliott, P and Scott, J and Prokopenko, I and Cebola, I and Loh, M and Lenhard, B and Batterham, RL and Bell, JT and Chambers, JC and Kooner, JS and Scott, WR},
doi = {10.1038/s41467-023-38439-z},
journal = {Nature Communications},
pages = {1--20},
title = {Integrative genomic analyses in adipocytes implicate DNA methylation in human obesity and diabetes},
url = {http://dx.doi.org/10.1038/s41467-023-38439-z},
volume = {14},
year = {2023}
}

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TY  - JOUR
AB  - 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 < 1 × 10-7). We connect obesity-associated methylation variations to transcriptomic changes at >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.
AU  - McAllan,L
AU  - Baranasic,D
AU  - Villicaña,S
AU  - Brown,S
AU  - Zhang,W
AU  - Lehne,B
AU  - Adamo,M
AU  - Jenkinson,A
AU  - Elkalaawy,M
AU  - Mohammadi,B
AU  - Hashemi,M
AU  - Fernandes,N
AU  - Lambie,N
AU  - Williams,R
AU  - Christiansen,C
AU  - Yang,Y
AU  - Zudina,L
AU  - Lagou,V
AU  - Tan,S
AU  - Castillo-Fernandez,J
AU  - King,JWD
AU  - Soong,R
AU  - Elliott,P
AU  - Scott,J
AU  - Prokopenko,I
AU  - Cebola,I
AU  - Loh,M
AU  - Lenhard,B
AU  - Batterham,RL
AU  - Bell,JT
AU  - Chambers,JC
AU  - Kooner,JS
AU  - Scott,WR
DO  - 10.1038/s41467-023-38439-z
EP  - 20
PY  - 2023///
SN  - 2041-1723
SP  - 1
TI  - Integrative genomic analyses in adipocytes implicate DNA methylation in human obesity and diabetes
T2  - Nature Communications
UR  - http://dx.doi.org/10.1038/s41467-023-38439-z
UR  - https://www.ncbi.nlm.nih.gov/pubmed/37188674
UR  - https://www.nature.com/articles/s41467-023-38439-z
UR  - http://hdl.handle.net/10044/1/104389
VL  - 14
ER  -

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