Ma, BaoshanWilker, ElissaWillis-Owen, Saffron A. G.Byun, Hyang-MinWong, Kenny C. C.Motta, ValeriaBaccarelli, Andrea A.Schwartz, JoelCookson, William O. C. M.Khabbaz, KamalMittleman, MurrayMoffatt, Miriam F.Liang, Liming2014-05-062014Ma, B., E. H. Wilker, S. A. G. Willis-Owen, H. Byun, K. C. C. Wong, V. Motta, A. A. Baccarelli, et al. 2014. “Predicting DNA methylation level across human tissues.” Nucleic Acids Research 42 (6): 3515-3528. doi:10.1093/nar/gkt1380. http://dx.doi.org/10.1093/nar/gkt1380.0305-1048http://nrs.harvard.edu/urn-3:HUL.InstRepos:12152862Differences 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-to-artery prediction; from 0.39 to 0.95 for PBL-to-atrium; 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 hard-to-access tissues (e.g. atrium) and might enable non-invasive disease screening using epigenetic profiles.en-USJournal Article2014-05-0610.1093/nar/gkt1380