| URL: | http://epigenetics.essex.ac.uk/bloodbrain |
| Full name: | Blood Brain DNA Methylation Comparison Tool |
| Description: | While it is widely acknowledged that the choice of a relevant tissue is imperative for the biological interpretation of epigenome-wide association studies (EWAS), obtaining such samples, particularly in the numbers required to overcome the multiple testing burden of testing loci genome-wide, can be challenging. This is true for studies of brain disorders, such as schizophrenia, Alzheimer's disease and autism, where often alternative, easily obtainable peripheral tissues such as blood or buccal samples are used instead. In order to establish the relevance of associated loci, these are subsequently followed up in available cohorts of brain tissue. Here we introduce an online tool which allows the user to perform this secondary analysis by investigating the correlation of DNA methylation in blood with four brain regions (prefrontal cortex, entorhinal cortex, superior temporal gyrus and cerebellum) from 71-75 matched samples for all probes present on the Illumina 450K Beadchip array. |
| Year founded: | 2015 |
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| Accessibility: |
Accessible
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| Country/Region: | United Kingdom |
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| University/Institution: | University of Exeter |
| Address: | University of Exeter Medical School, University of Exeter, Exeter, UK |
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| Country/Region: | United Kingdom |
| Contact name (PI/Team): | Eilis Hannon |
| Contact email (PI/Helpdesk): | E.J.Hannon@exeter.ac.uk |
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Interindividual methylomic variation across blood, cortex, and cerebellum: implications for epigenetic studies of neurological and neuropsychiatric phenotypes. [PMID: 26457534]
Given the tissue-specific nature of epigenetic processes, the assessment of disease-relevant tissue is an important consideration for epigenome-wide association studies (EWAS). Little is known about whether easily accessible tissues, such as whole blood, can be used to address questions about interindividual epigenomic variation in inaccessible tissues, such as the brain. We quantified DNA methylation in matched DNA samples isolated from whole blood and 4 brain regions (prefrontal cortex, entorhinal cortex, superior temporal gyrus, and cerebellum) from 122 individuals. We explored co-variation between tissues and the extent to which methylomic variation in blood is predictive of interindividual variation identified in the brain. For the majority of DNA methylation sites, interindividual variation in whole blood is not a strong predictor of interindividual variation in the brain, although the relationship with cortical regions is stronger than with the cerebellum. Variation at a subset of probes is strongly correlated across tissues, even in instances when the actual level of DNA methylation is significantly different between them. A substantial proportion of this co-variation, however, is likely to result from genetic influences. Our data suggest that for the majority of the genome, a blood-based EWAS for disorders where brain is presumed to be the primary tissue of interest will give limited information relating to underlying pathological processes. These results do not, however, discount the utility of using a blood-based EWAS to identify biomarkers of disease phenotypes manifest in the brain. We have generated a searchable database for the interpretation of data from blood-based EWAS analyses ( http://epigenetics.essex.ac.uk/bloodbrain/). |