title: Personalized epigenomic signatures that are stable over time and covary with body mass index.
abstract: The epigenome consists of non-sequence-based modifications, such as DNA methylation, that are heritable during cell division and that may affect normal phenotypes and predisposition to disease. Here, we have performed an unbiased genome-scale analysis of ~4 million CpG sites in 74 individuals with comprehensive array-based relative methylation (CHARM) analysis. We found 227 regions that showed extreme interindividual variability [variably methylated regions (VMRs)] across the genome, which are enriched for developmental genes based on Gene Ontology analysis. Furthermore, half of these VMRs were stable within individuals over an average of 11 years, and these VMRs defined a personalized epigenomic signature. Four of these VMRs showed covariation with body mass index consistently at two study visits and were located in or near genes previously implicated in regulating body weight or diabetes. This work suggests an epigenetic strategy for identifying patients at risk of common disease.
authors.affiliation: Center for Epigenetics, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA. afeinberg@jhu.edu
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Feinberg
authors.forename: Rafael A
authors.initials: RA
authors.lastname: Irizarry
authors.forename: Delphine
authors.initials: D
authors.lastname: Fradin
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Aryee
authors.forename: Peter
authors.initials: P
authors.lastname: Murakami
authors.forename: Thor
authors.initials: T
authors.lastname: Aspelund
authors.forename: Gudny
authors.initials: G
authors.lastname: Eiriksdottir
authors.forename: Tamara B
authors.initials: TB
authors.lastname: Harris
authors.forename: Lenore
authors.initials: L
authors.lastname: Launer
authors.forename: Vilmundur
authors.initials: V
authors.lastname: Gudnason
authors.forename: M Daniele
authors.initials: MD
authors.lastname: Fallin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics*; D057890:Epigenomics; D006801:Humans; D013997:Time Factors