EUROPEAN SOCIETY FOR BIOMEDICAL RESEARCH ON ALCOHOLISM. 12â15 SEPTEMBER 2015. VALENCIA, SPAIN. SY22-2. EPIGENOME IN THE BRAIN ...
Alcohol and Alcoholism, 2015, 50(S1) i1–i67
Abstracts
ESBRA 2015 EUROPEAN SOCIETY FOR BIOMEDICAL RESEARCH ON ALCOHOLISM 12–15 SEPTEMBER 2015 VALENCIA, SPAIN
SY22-2 EPIGENOME IN THE BRAIN OF HUMAN ALCOHOLICS: GENETICALLY-REGULATED TRAJECTORIES OF DNA METHYLATION D. Sarkisyan, I. Bazov, T. Yakovleva, and G. Bakalkin Dept. Pharmaceutical Biosciences, Uppsala University, Sweden The vulnerability to alcohol is determined by genetic, environmental and epigenetic factors. We aim to identify variations in the epigenome that is associated to alcoholism by interrogating DNA methylation sites across the genome. We matched 39 individuals with alcoholism and 47 controls of European descent for age and gender, and analyzed genome-wide methylation of total tissue DNA in the dl-PFC and ventral striatum from all subjects, and neuronal and non-neuronal DNA separately in the dl-PFC of 16 alcoholics and 16 controls, by Illumina’s HumanMethylation450 BeadChip
assays. Differentially methylated CpGs (DMPs) and CpG regions (DMRs) in alcoholics were identified. Data will be presented on DMPs / DMRs showing significant effects in both brain tissues, their clustering in modules of inter-correlated CpGs, and association of these modules with alcohol abuse / dependence. In the course of analysis, clusters of CpGs showing highly correlated methylation were identified. Such clusters may serve as a source of epigenetic variation and give insights into the epigenome structure and function. Specifically, in the promoter of the prodynorphin gene that plays a critical role in addictive disorders, the CpG cluster with highly correlated methylation levels overlaps with the short CpG island. Coherence in methylation at this cluster a) correlates with gene expression across human brain areas, and b) differ between alcoholics and controls that may underlie changes in transcription of this gene. In summary, we observed an association between DNA methylation and disease status that overall highlights genes implicated in neuronal functioning. FAS, VR, FORMAS.
