Predicting DNA methylation level across human tissues

Baoshan Ma, Elissa H. Wilker, Saffron A G Willis-Owen, Hyang Min Byun, Kenny C C Wong, Valeria Motta, Andrea A. Baccarelli, Joel Schwartz, William O C M Cookson, Kamal Khabbaz, Murray A. Mittleman, Miriam F. Moffatt, Liming Liang

Research output: Contribution to journalArticlepeer-review


Differences in methylation across tissues are critical to cell differentiation and are key to understanding the role of epigenetics in complex diseases. In this investigation, we found that locus-specific methylation differences between tissues are highly consistent across individuals. We developed a novel statistical model to predict locus-specific methylation in target tissue based on methylation in surrogate tissue. The method was evaluated in publicly available data and in two studies using the latest IlluminaBeadChips: a childhood asthma study with methylation measured in both peripheral blood leukocytes (PBL) and lymphoblastoid cell lines; and a study of postoperative atrial fibrillation with methylation in PBL, atrium and artery. We found that our method can greatly improve accuracy of cross-tissue prediction at CpG sites that are variable in the target tissue [R2 increases from 0.38 (original R2 between tissues) to 0.89 for PBL-toartery prediction; from 0.39 to 0.95 for PBL-toatrium; and from 0.81 to 0.98 for lymphoblastoid cell line-to-PBL based on cross-validation, and confirmed using cross-study prediction]. An extended model with multiple CpGs further improved performance. Our results suggest that large-scale epidemiology studies using easy-to-access surrogate tissues (e.g. blood) could be recalibrated to improve understanding of epigenetics in hardto- access tissues (e.g. atrium) and might enable non-invasive disease screening using epigenetic profiles.

Original languageEnglish
Pages (from-to)3515-3528
Number of pages14
JournalNucleic Acids Research
Issue number6
Publication statusPublished - 2014

ASJC Scopus subject areas

  • Genetics


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