Validation of a DNA methylation reference panel for the estimation of nucleated cells types in cord blood |
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| Authors: | Andres Cardenas Catherine Allard Myriam Doyon E. Andres Houseman Kelly M. Bakulski Patrice Perron |
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| Affiliation: | 1. Department of Population Medicine, Harvard Pilgrim Health Care Institute, Harvard Medical School, Boston, MA, USA;2. Centre de Recherche du Center Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada;3. College of Public Health and Human Sciences, Oregon State University, Corvallis, OR, USA;4. Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA;5. Department of Medicine, Faculty of Medicine and Life Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada |
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| Abstract: | Cord blood is widely used as surrogate tissue in epigenome-wide association studies of prenatal conditions. Cell type composition variation across samples can be an important confounder of epigenome-wide association studies in blood that constitute a mixture of cells. We evaluated a newly developed cord blood reference panel to impute cell type composition from DNA methylation levels, including nucleated red blood cells (nRBCs). We estimated cell type composition from 154 unique cord blood samples with available DNA methylation data as well as direct measurements of nucleated cell types. We observed high correlations between the estimated and measured composition for nRBCs (r = 0.92, R2 = 0.85), lymphocytes (r = 0.77, R2 = 0.58), and granulocytes (r = 0.72, R2 = 0.52), and a moderate correlation for monocytes (r = 0.51, R2 = 0.25) as well as relatively low root mean square errors from the residuals ranging from 1.4 to 5.4%. These results validate the use of the cord blood reference panel and highlight its utility and limitations for epidemiological studies. |
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| Keywords: | Cord blood DNA methylation EWAS birth cohort Illumina 450K nucleated red blood cells white blood cell composition |
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