Dissecting features of epigenetic variants underlying cardiometabolic risk using full-resolution epigenome profiling in regulatory elements

Fiona Allum, Åsa K. Hedman, Xiaojian Shao, Warren A. Cheung, Jinchu Vijay, Frédéric Guénard, Tony Kwan, Marie-Michelle Simon, Bing Ge, Cristiano Moura, Elodie Boulier, Lars Rönnblom, Sasha Bernatsky, Mark Lathrop, Mark I. McCarthy, Panos Deloukas, André Tchernof, Tomi Pastinen, Marie-Claude Vohl and Elin Grundberg ()
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Fiona Allum: McGill University
Åsa K. Hedman: Karolinska Institute
Xiaojian Shao: McGill University
Warren A. Cheung: McGill University
Jinchu Vijay: McGill University
Frédéric Guénard: Université Laval
Tony Kwan: McGill University
Marie-Michelle Simon: McGill University
Bing Ge: McGill University
Cristiano Moura: McGill University
Elodie Boulier: McGill University
Lars Rönnblom: Uppsala University
Sasha Bernatsky: McGill University
Mark Lathrop: McGill University
Mark I. McCarthy: University of Oxford
Panos Deloukas: Queen Mary University of London
André Tchernof: Université Laval
Tomi Pastinen: McGill University
Marie-Claude Vohl: Université Laval
Elin Grundberg: McGill University

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-09184-z

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