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Characterization of functional methylomes by next-generation capture sequencing identifies novel disease-associated variants
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2015 (engelsk)Inngår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 6, artikkel-id 7211Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Most genome-wide methylation studies (EWAS) of multifactorial disease traits use targeted arrays or enrichment methodologies preferentially covering CpG-dense regions, to characterize sufficiently large samples. To overcome this limitation, we present here a new customizable, cost-effective approach, methylC-capture sequencing (MCC-Seq), for sequencing functional methylomes, while simultaneously providing genetic variation information. To illustrate MCC-Seq, we use whole-genome bisulfite sequencing on adipose tissue (AT) samples and public databases to design AT-specific panels. We establish its efficiency for high-density interrogation of methylome variability by systematic comparisons with other approaches and demonstrate its applicability by identifying novel methylation variation within enhancers strongly correlated to plasma triglyceride and HDL-cholesterol, including at CD36. Our more comprehensive AT panel assesses tissue methylation and genotypes in parallel at ∼4 and ∼3 M sites, respectively. Our study demonstrates that MCC-Seq provides comparable accuracy to alternative approaches but enables more efficient cataloguing of functional and disease-relevant epigenetic and genetic variants for large-scale EWAS.

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2015. Vol. 6, artikkel-id 7211
HSV kategori
Forskningsprogram
Medicinsk vetenskap
Identifikatorer
URN: urn:nbn:se:uu:diva-253885DOI: 10.1038/ncomms8211ISI: 000355537600002PubMedID: 26021296OAI: oai:DiVA.org:uu-253885DiVA, id: diva2:816392
Tilgjengelig fra: 2015-06-03 Laget: 2015-06-03 Sist oppdatert: 2017-12-04bibliografisk kontrollert

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