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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 ~200 adipose tissue and matched blood samples (Ntotal~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 ~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.

Original publication

DOI

10.1038/s41467-019-09184-z

Type

Journal article

Journal

Nat Commun

Publication Date

14/03/2019

Volume

10

Keywords

Adipose Tissue, Adult, Aged, Cardiovascular Diseases, CpG Islands, DNA Methylation, Epigenesis, Genetic, Epigenomics, Female, Gene Expression Profiling, Genome, Human, Genome-Wide Association Study, High-Throughput Nucleotide Sequencing, Humans, Lipids, Male, Metabolic Diseases, Middle Aged, Polymorphism, Single Nucleotide, Regulatory Sequences, Nucleic Acid, Sequence Analysis, DNA