Epigenetic Signatures of Smoking in Five Brain Regions

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; Marcella Rietschel

doi:10.3390/jpm12040566

Journal of Personalized Medicine (Apr 2022)

Epigenetic Signatures of Smoking in Five Brain Regions

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,
Marcella Rietschel

Affiliations

Lea Zillich: Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany
Eric Poisel: Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany
Fabian Streit: Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany
Josef Frank: Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany
Gabriel R. Fries: Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77054, USA
Jerome C. Foo: Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany
Marion M. Friske: Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68159 Mannheim, Germany
Lea Sirignano: Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany
Anita C. Hansson: Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68159 Mannheim, Germany
Markus M. Nöthen: Institute of Human Genetics, School of Medicine & University Hospital Bonn, University of Bonn, 53127 Bonn, Germany
Stephanie H. Witt: Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany
Consuelo Walss-Bass: Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77054, USA
Rainer Spanagel: Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68159 Mannheim, Germany
Marcella Rietschel: Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany

DOI: https://doi.org/10.3390/jpm12040566
Journal volume & issue: Vol. 12, no. 4
p. 566

Abstract

Read online

(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.

Published in Journal of Personalized Medicine

ISSN: 2075-4426 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine
Website: http://www.mdpi.com/journal/jpm

About the journal

Abstract

Keywords