Journal
EPIGENOMICS
Volume 9, Issue 1, Pages 13-20Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/epi-2016-0091
Keywords
DNA methylation; estimation of cell proportions; Infinium 450K; KAROLA; leukocyte composition; LOLIPOP; white-blood cell distribution
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Funding
- National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre
- Imperial College Healthcare NHS Trust
- British Heart Foundation [SP/04/002]
- Medical Research Council [G0601966, G0700931]
- Wellcome Trust [084723/Z/08/Z]
- National Institute for Health Research [RP-PG-0407-10371]
- EU FP7 (EpiMigrant) [279143]
- Action on Hearing Loss [G51]
- National Institutes of Health Research (NIHR) [RP-PG-0407-10371] Funding Source: National Institutes of Health Research (NIHR)
- Wellcome Trust [084723/Z/08/Z] Funding Source: Wellcome Trust
- Medical Research Council [G0700931, G0601966] Funding Source: researchfish
- National Institute for Health Research [RP-PG-0407-10371] Funding Source: researchfish
- MRC [G0700931, G0601966] Funding Source: UKRI
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Aim: Whole-blood DNA methylation depends on the underlying leukocyte composition and confounding hereby is a major concern in epigenome-wide association studies. Cell counts are often missing or may not be feasible. Computational approaches estimate leukocyte composition from DNA methylation based on reference datasets of purified leukocytes. We explored the possibility to train such a model on whole-blood DNA methylation and cell counts without the need for purification. Materials & methods: Using whole-blood DNA methylation and corresponding five-part cell counts from 2445 participants from the London Life Sciences Prospective Population Study, a model was trained on a subset of 175 subjects and evaluated on the remaining. Results: Correlations between cell counts and estimated cell proportions were high (neutrophils 0.85, eosinophils 0.88, basophils 0.02, lymphocytes 0.84, monocytes 0.55) and estimated proportions explained more variance in whole-blood DNA methylation levels than counts. Conclusion: Our model provided precise estimates for the common cell types.
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