Characterization of functional methylomes by next-generation capture sequencing identifies novel disease-associated variants

Authors: Allum, Fiona; Shao, Xiaojian; Guénard, Frédéric; Simon, Marie-Michelle; Busche, Stephan; Caron, Maxime; Lambourn, John; Lessard, Julie; Tandre, Karolina; Hedman, Asa K.; Kwan, Tony; Ge, Bing; Rönnblom, Lars; McCarthy, Mark I.; Deloukas, Panos; Richmond, Todd; Burgess, Daniel; Spector, T. D. (Timothy David); Tchernof, André; Marceau, Simon; Lathrop, Mark; Vohl, Marie-Claude; Pastinen, Tomi; Grundberg, Elin
Abstract: Most genome-wide methylation studies (EWAS) of multifactorial disease traits use targetedarrays or enrichment methodologies preferentially covering CpG-dense regions, tocharacterize sufficiently large samples. To overcome this limitation, we present here a newcustomizable, cost-effective approach, methylC-capture sequencing (MCC-Seq), forsequencing functional methylomes, while simultaneously providing genetic variationinformation. To illustrate MCC-Seq, we use whole-genome bisulfite sequencing on adiposetissue (AT) samples and public databases to design AT-specific panels. We establish itsefficiency for high-density interrogation of methylome variability by systematic comparisonswith other approaches and demonstrate its applicability by identifying novel methylationvariation within enhancers strongly correlated to plasma triglyceride and HDL-cholesterol,including atCD36. Our more comprehensive AT panel assesses tissue methylation andgenotypes in parallel atB4 andB3 M sites, respectively. Our study demonstrates thatMCC-Seq provides comparable accuracy to alternative approaches but enables more efficientcataloguing of functional and disease-relevant epigenetic and genetic variants for large-scale EWAS.
Document Type: Article de recherche
Issue Date: 28 February 2015
Open Access Date: 7 October 2020
Document version: VoR
Creative Commons Licence: https://creativecommons.org/licenses/by/4.0
Permalink: http://hdl.handle.net/20.500.11794/66730
This document was published in: Nature Communications, Vol. 6, 7211-7221 (2015)
https://doi.org/10.1038/ncomms8211
Nature Publishing Group
Alternative version: 10.1038/ncomms8211
26021296
Collection:Articles publiés dans des revues avec comité de lecture

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