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. 2010 Sep 15;2(49):49ra67.
doi: 10.1126/scitranslmed.3001262.

Personalized epigenomic signatures that are stable over time and covary with body mass index

Andrew P Feinberg  1 , Rafael A Irizarry, Delphine Fradin, Martin J Aryee, Peter Murakami, Thor Aspelund, Gudny Eiriksdottir, Tamara B Harris, Lenore Launer, Vilmundur Gudnason, M Daniele Fallin
Affiliations

Personalized epigenomic signatures that are stable over time and covary with body mass index

Andrew P Feinberg et al. Sci Transl Med. .

Erratum in

  • Sci Transl Med. 2011 Jan 12;3(65):65er1

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.

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Figures

Fig. 1
Fig. 1
Distribution of intraindividual change in methylation over time at VMRs. Mixture distribution analysis shows that Dk, the average absolute value of intraindividual differences in methylation over time for VMR k, fits two underlying curves. Green, stable showing little change; orange, dynamic showing larger changes. Ambiguous is intermediate in Dk.
Fig. 2
Fig. 2
Similarity between individuals based on VMR methylation. (A) Dendogram based on clustering applied to methylation profiles at all 227 VMRs. (B) Dendogram based on clustering applied to methylation profiles using only the 119 stable VMRs. Numbers represent individual identification numbers.
Fig. 3
Fig. 3
Methylation curves at the gene PM20D1. Methylation curves for visit 7 and visit 6 data. Dashed lines are individual methylation curves. Solid lines are average curves by obese (blue) and normal (red) groups. The green line indicates the boundaries of the VMR. CpG density is shown in the third panel, with CpG islands marked in orange. Gene location is shown in the bottom panel.
Fig. 4
Fig. 4
Correlations between methylation and BMI at six BMI-related VMRs. Points are individual IDs. Blue indicates visit 7; red indicates visit 6.
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References

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