GeMes, clusters of DNA methylation under genetic control, can inform genetic and epigenetic analysis of disease

Yun Liu, Xin Li, Martin J. Aryee, Tomas J. Ekström, Leonid Padyukov, Lars Klareskog, Amy Vandiver, Ann Zenobia Moore, Toshiko Tanaka, Luigi Ferrucci, M. Daniele Fallin, Andrew P. Feinberg

Research output: Contribution to journalArticle

Abstract

Epigenetic marks such as DNA methylation have generated great interest in the study of human disease. However, studies of DNA methylation have not established population-epigenetics principles to guide design, efficient statistics, or interpretation. Here, we show that the clustering of correlated DNA methylation at CpGs was similar to that of linkage-disequilibrium (LD) correlation in genetic SNP variation but for much shorter distances. Some clustering of methylated CpGs appeared to be genetically driven. Further, a set of correlated methylated CpGs related to a single SNP-based LD block was not always physically contiguous - segments of uncorrelated methylation as long as 300 kb could be interspersed in the cluster. Thus, we denoted these sets of correlated CpGs as GeMes, defined as potentially noncontiguous methylation clusters under the control of one or more methylation quantitative trait loci. This type of correlated methylation structure has implications for both biological functions of DNA methylation and for the design, analysis, and interpretation of epigenome-wide association studies.

Original languageEnglish (US)
Pages (from-to)485-495
Number of pages11
JournalAmerican journal of human genetics
Volume94
Issue number4
DOIs
StatePublished - Apr 3 2014

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Liu, Y., Li, X., Aryee, M. J., Ekström, T. J., Padyukov, L., Klareskog, L., Vandiver, A., Moore, A. Z., Tanaka, T., Ferrucci, L., Fallin, M. D., & Feinberg, A. P. (2014). GeMes, clusters of DNA methylation under genetic control, can inform genetic and epigenetic analysis of disease. American journal of human genetics, 94(4), 485-495. https://doi.org/10.1016/j.ajhg.2014.02.011