期刊
NATURE COMMUNICATIONS
卷 6, 期 -, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/ncomms8211
关键词
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资金
- Canadian Institute of Health Research (CIHR) team grant [TEC-128093]
- CIHR funded Epigeneome Mapping Centre at McGill University [EP1-120608]
- Swedish Research Council
- Knut and Alice Wallenberg Foundation
- Torsten Soderberg Foundation
- Research Institute of the McGill University Health Center (MUHC)
- Heart and Stroke Foundation of Canada
- Canada Research Chair in Genomics Applied to Nutrition and Health
- Canada Research Chair Tier 2 award
- Wellcome Trust [081917/Z/07/Z]
- core funding for the Wellcome Trust Centre for Human Genetics [090532]
- European Community's Seventh Framework Programme (FP7)
- National Institute for Health Research (NIHR)
- King's College London
- ERC Advanced Principal Investigator award
- MRC [G0600717, MC_UU_12012/1] Funding Source: UKRI
- Wellcome Trust [081917/Z/07/Z] Funding Source: Wellcome Trust
- Medical Research Council [G0600717, MC_UU_12012/1, MC_UU_12012/5/B, G0600717B] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0513-10109, NF-SI-0507-10380, NF-SI-0611-10099] Funding Source: researchfish
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 similar to 4 and similar to 3M 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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