Personalized Epigenomic Signatures That Are Stable Over Time and Covary with Body Mass Index

被引：233

作者：

Feinberg, Andrew P. ^{[1
,2
]}

Irizarry, Rafael A. ^{[1
,3
]}

Fradin, Delphine ^{[1
,2
]}

Aryee, Martin J. ^{[1
,4
]}

Murakami, Peter ^{[1
,2
]}

Aspelund, Thor ^{[5
,6
]}

Eiriksdottir, Gudny ^{[5
]}

Harris, Tamara B. ^{[7
]}

Launer, Lenore ^{[7
]}

Gudnason, Vilmundur ^{[5
,6
]}

Fallin, M. Daniele ^{[1
,8
]}

机构：

[1] Johns Hopkins Sch Med, Ctr Epigenet, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA

[3] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA

[4] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA

[5] Iceland Heart Assoc, IS-201 Kopavogur, Iceland

[6] Univ Iceland, Reykjavik, Iceland

[7] NIA, Intramural Res Program, Baltimore, MD 21205 USA

[8] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA

来源：

SCIENCE TRANSLATIONAL MEDICINE | 2010年 / 2卷 / 49期

关键词：

COMMON HUMAN-DISEASE; DNA METHYLATION; EPIGENETICS; CANCER; SUSCEPTIBILITY; OBESITY; AGE; OVERWEIGHT; EXPRESSION; SORCS1;

D O I：

10.1126/scitranslmed.3001262

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 similar to 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.

引用

页数：7

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