Dissecting features of epigenetic variants underlying cardiometabolic risk using full-resolution epigenome profiling in regulatory elements.
Nat Commun
; 10(1): 1209, 2019 03 14.
Article
em En
| MEDLINE
| ID: mdl-30872577
ABSTRACT
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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Doenças Cardiovasculares
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Sequências Reguladoras de Ácido Nucleico
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Ilhas de CpG
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Epigênese Genética
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Doenças Metabólicas
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article