Journal
NATURE COMMUNICATIONS
Volume 10, Issue -, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-019-09184-z
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Funding
- Canadian Institute of Health Research (CIHR) [TEC-128093]
- CIHR Foundation [148391]
- CIHR [EP1-120608]
- Fonds de recherche du Quebec (FRSQ)
- Swedish Rheumatism Association
- King Gustaf V's 80-years Foundation
- Swedish Research Council
- Wallenberg Foundation
- NIHR Oxford Biomedical Research Center
- Wellcome Trust [081917/Z/07/Z]
- Wellcome Trust
- European Community's Seventh Framework Program (FP7/2007-2013)
- National Institute for Health Research (NIHR)
- King's College London
- [090532]
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Sparse profiling of CpG methylation in blood by microarrays has identified epigenetic links to common diseases. Here we apply methylC-capture sequencing (MCC-Seq) in a clinical population of similar to 200 adipose tissue and matched blood samples (N-total similar to 400), providing high- resolution methylation profiling (>1.3 M CpGs) at regulatory elements. We link methylation to cardiometabolic risk through associations to circulating plasma lipid levels and identify lipid-associated CpGs with unique localization patterns in regulatory elements. We show distinct features of tissue-specific versus tissue-independent lipid-linked regulatory regions by contrasting with parallel assessments in similar to 800 independent adipose tissue and blood samples from the general population. We follow-up on adipose-specific regulatory regions under (1) genetic and (2) epigenetic (environmental) regulation via integrational studies. Overall, the comprehensive sequencing of regulatory element methylomes reveals a rich landscape of functional variants linked genetically as well as epigenetically to plasma lipid traits.
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