DNA methylation differences in cortical grey and white matter in schizophrenia

Author:

Berdenis van Berlekom Amber12ORCID,Notman Nina1,Sneeboer Marjolein AM12,Snijders Gijsje JLJ13ORCID,Houtepen Lotte C1,Nispeling Danny M1,He Yujie12,Dracheva Stella34ORCID,Hol Elly M2,Kahn René S134,de Witte Lot D13,Boks Marco P1ORCID,

Affiliation:

1. Department of Psychiatry, Brain Center University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands

2. Department of Translational Neuroscience, Brain Center University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands

3. Mental Illness Research, Education, & Clinical Center (VISN 2 South), James J Peters VA Medical Center, Bronx, NY 10468, USA

4. Psychiatric Donor Program of The Netherlands Brain Bank (NBB-PSY), Amsterdam, The Netherlands

Abstract

Aim: Identify grey- and white-matter-specific DNA-methylation differences between schizophrenia (SCZ) patients and controls in postmortem brain cortical tissue. Materials & methods: Grey and white matter were separated from postmortem brain tissue of the superior temporal and medial frontal gyrus from SCZ (n = 10) and control (n = 11) cases. Genome-wide DNA-methylation analysis was performed using the Infinium EPIC Methylation Array (Illumina, CA, USA). Results: Four differentially methylated regions associated with SCZ status and tissue type (grey vs white matter) were identified within or near KLF9, SFXN1, SPRED2 and ALS2CL genes. Gene-expression analysis showed differential expression of KLF9 and SFXN1 in SCZ. Conclusion: Our data show distinct differences in DNA methylation between grey and white matter that are unique to SCZ, providing new leads to unravel the pathogenesis of SCZ.

Funder

Veteran Affairs

National Institute Health

Publisher

Future Medicine Ltd

Subject

Cancer Research,Genetics

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