title: GeMes, clusters of DNA methylation under genetic control, can inform genetic and epigenetic analysis of disease.
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.
authors.affiliation: Center for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Center for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Center for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02114, USA.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Aryee
authors.affiliation: Center for Molecular Medicine, Karolinska Institutet and University Hospital, Stockholm 17176, Sweden; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm 17176, Sweden.
authors.forename: Tomas J
authors.initials: TJ
authors.lastname: Ekström
authors.affiliation: Center for Molecular Medicine, Karolinska Institutet and University Hospital, Stockholm 17176, Sweden; Rheumatology Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm 17176, Sweden.
authors.forename: Leonid
authors.initials: L
authors.lastname: Padyukov
authors.affiliation: Center for Molecular Medicine, Karolinska Institutet and University Hospital, Stockholm 17176, Sweden; Rheumatology Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm 17176, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Klareskog
authors.affiliation: Center for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Vandiver
authors.affiliation: Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: Ann Zenobia
authors.initials: AZ
authors.lastname: Moore
authors.affiliation: Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: Toshiko
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.affiliation: Center for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Deparment of Mental Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA. Electronic address: dfallin@jhsph.edu.
authors.forename: M Daniele
authors.initials: MD
authors.lastname: Fallin
authors.affiliation: Center for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: afeinberg@jhu.edu.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Feinberg
mesh_terms: D019175:DNA Methylation; D044127:Epigenesis, Genetic; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D012907:Smoking / Q000235:genetics