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. 2013 Aug;5(4):367-77.
doi: 10.2217/epi.13.36.

Testing two models describing how methylome-wide studies in blood are informative for psychiatric conditions

Karolina A Aberg  1 , Lin Y Xie, Joseph L McClay, Srilaxmi Nerella, Sarah Vunck, Sarah Snider, Patrick M Beardsley, Edwin J C G van den Oord
Affiliations

Testing two models describing how methylome-wide studies in blood are informative for psychiatric conditions

Karolina A Aberg et al. Epigenomics. 2013 Aug.

Abstract

Aim: As the primary relevant tissue (brain) for psychiatric disorders is commonly not available, we aimed to investigate whether blood can be used as a proxy in methylation studies on the basis of two models. In the 'signature' model methylation-disease associations occur because a disease-causing factor affected methylation in the blood. In the 'mirror-site' model the methylation status in the blood is correlated with the corresponding disease-causing site in the brain. MATERIALS, METHODS & RESULTS: Methyl-binding domain enrichment and next-generation sequencing of the blood, cortex and hippocampus from four haloperidol-treated and ten untreated C57BL/6 mice revealed high levels of correlation in methylation across tissues. Despite the treatment inducing a large number of methylation changes, this correlation remains high.

Conclusion: Our results show that, consistent with the signature model, factors that affect brain processes (i.e., haloperidol) leave biomarker signatures in the blood and, consistent with the mirror-site model, the methylation status of many sites in the blood mirror those in the brain.

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Figures

Figure 1
Figure 1. Two path diagrams describing how methylation studies in blood are informative for psychiatric conditions
In neither model do we assume that the methylation mark observed in blood is causing the development of the disease. The white boxes indicate an association between features. The curved arrow indicates correlation. (A) The signature model: an event causes a methylation change in blood that is associated with the disease. (B) The mirror-site model: a methylation change in blood is associated with the disease. The site is also correlated with the methylation mark for the corresponding site in the brain, which may help reveal functional information related to the disease development.
Figure 2
Figure 2. Sample correlations for each mouse
Sample correlations for the three tissue combinations for each of the untreated (1–10) and treated (11–14) mice are shown on the left and right side of the vertical line, respectively. Sample correlations are given with (solid lines) and without (dashed lines) CpG density normalization.
Figure 3
Figure 3. Site correlation for the three tissue combinations for all methylated CpGs in a balanced set of untreated and treated mice
The x-axis shows the site correlation and the y-axis shows the density of the distribution.
See this image and copyright information in PMC

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Website

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