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Dissecting features of epigenetic variants underlying cardiometabolic risk using full-resolution epigenome profiling in regulatory elements
McGill Univ, Dept Human Genet, Montreal, PQ H3A 0C7, Canada;McGill Univ, Montreal, PQ H3A 0G1, Canada;Genome Quebec Innovat Ctr, Montreal, PQ H3A 0G1, Canada.
Karolinska Inst, Cardiovasc Med Unit, Dept Med Solna, S-17176 Stockholm, Sweden.
McGill Univ, Dept Human Genet, Montreal, PQ H3A 0C7, Canada;McGill Univ, Montreal, PQ H3A 0G1, Canada;Genome Quebec Innovat Ctr, Montreal, PQ H3A 0G1, Canada.
McGill Univ, Dept Human Genet, Montreal, PQ H3A 0C7, Canada;McGill Univ, Montreal, PQ H3A 0G1, Canada;Genome Quebec Innovat Ctr, Montreal, PQ H3A 0G1, Canada;Childrens Mercy Hosp & Clin, Kansas City, MO 64108 USA.
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2019 (engelsk)Inngår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 10, artikkel-id 1209Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

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.

sted, utgiver, år, opplag, sider
2019. Vol. 10, artikkel-id 1209
HSV kategori
Identifikatorer
URN: urn:nbn:se:uu:diva-380447DOI: 10.1038/s41467-019-09184-zISI: 000461161500005PubMedID: 30872577OAI: oai:DiVA.org:uu-380447DiVA, id: diva2:1300162
Forskningsfinansiär
Swedish Research CouncilEU, FP7, Seventh Framework ProgrammeTilgjengelig fra: 2019-03-28 Laget: 2019-03-28 Sist oppdatert: 2019-03-28bibliografisk kontrollert

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