Epigenetic signatures of smoking in five brain regions

(1) Background: Epigenome-wide association studies (EWAS) in peripheral blood have repeatedly found associations between tobacco smoking and aberrant DNA methylation (DNAm), but little is known about DNAm signatures of smoking in the human brain, which may contribute to the pathophysiology of addict...

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Main Authors: Zillich, Lea (Author) , Zillich, Eric (Author) , Streit, Fabian (Author) , Frank, Josef (Author) , Fries, Gabriel R. (Author) , Foo, Jerome Clifford (Author) , Friske, Marion M. (Author) , Sirignano, Lea (Author) , Hansson, Anita C. (Author) , Nöthen, Markus M. (Author) , Witt, Stephanie (Author) , Walss-Bass, Consuelo (Author) , Spanagel, Rainer (Author) , Rietschel, Marcella (Author)
Format: Article (Journal)
Language:English
Published: 2 April 2022
In: Journal of Personalized Medicine
Year: 2022, Volume: 12, Issue: 4, Pages: 1-12
ISSN:2075-4426
DOI:10.3390/jpm12040566
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.3390/jpm12040566
Verlag, kostenfrei, Volltext: https://www.mdpi.com/2075-4426/12/4/566
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Author Notes:Lea Zillich, Eric Poisel, Fabian Streit, Josef Frank, Gabriel R. Fries, Jerome C. Foo, Marion M. Friske, Lea Sirignano, Anita C. Hansson, Markus M. Nöthen, Stephanie H. Witt, Consuelo Walss-Bass, Rainer Spanagel and Marcella Rietschel

MARC

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520 |a (1) Background: Epigenome-wide association studies (EWAS) in peripheral blood have repeatedly found associations between tobacco smoking and aberrant DNA methylation (DNAm), but little is known about DNAm signatures of smoking in the human brain, which may contribute to the pathophysiology of addictive behavior observed in chronic smokers. (2) Methods: We investigated the similarity of DNAm signatures in matched blood and postmortem brain samples (n = 10). In addition, we performed EWASs in five brain regions belonging to the neurocircuitry of addiction: anterior cingulate cortex (ACC), Brodmann Area 9, caudate nucleus, putamen, and ventral striatum (n = 38-72). (3) Results: cg15925993 within the LOC339975 gene was epigenome-wide significant in the ACC. Of 16 identified differentially methylated regions, two (PRSS50 and LINC00612/A2M-AS1) overlapped between multiple brain regions. Functional enrichment was detected for biological processes related to neuronal development, inflammatory signaling and immune cell migration. Additionally, our results indicate the association of the well-known AHRR CpG site cg05575921 with smoking in the brain. (4) Conclusion: The present study provides further evidence of the strong relationship between aberrant DNAm and smoking. 
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