UTVEC KLINGSMÄSSIG NEUROEPIGENETIK VID ALKOHOLISM: profilering av DNA-metylering i hjärna och blod

Tidsperiod: 2020-01-01 till 2022-12-31

Projektledare: Georgy Bakalkin

Finansiär: Vetenskapsrådet

Bidragstyp: Projektbidrag

Budget: 2 400 000 SEK

We hypothesize that alterations in the epigenome in response to adverse events and / or alcohol binging in early life may be a critical factor contributing to risk and resilience to alcohol use disorders and alcoholism. These effects may be primarily mediated through stable changes in DNA methylation. In the first phase of our program (2012-2017) we have already created the unique large epigenetic, genotype and gene expression databank for adolescents from the prospective longitudinal European IMAGEN project, and for the large collections of postmortem specimens from human adolescents, young adults and adult alcoholics and controls. Analyzing these datasets by cutting edge bioinformatic tools we will first evaluate whether epigenetic mechanisms mediate effects of causal neuropsychosocial factors on adolescent alcohol misuse in IMAGEN sample. Second, we will assess the relevance of epigenetic signatures associated with these factors and alcohol misuse for the developmental and alcohol-associated human brain phenotypes (postmortem study). Third, we will examine whether the robust predictive epigenome features - the epigenetic age acceleration and the alcohol DNA methylation biomarker are associated with causal factors for alcohol misuse and predict adolescent binge drinking and adult alcoholism. Finally, we will explore if alcohol effects on the developing and adult human brain are generalized through epigenetic machinery controlling global patterns of DNA methylation.