Methylation patterns in whole blood correlate with symptoms in schizophrenia patients

Jingyu Liu, Jiayu Chen, Stefan Ehrlich, Esther Walton, Tonya White, Nora Perrone-Bizzozero, Juan Bustillo, Jessica A Turner, Vince D Calhoun

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

DNA methylation, one of the main epigenetic mechanisms to regulate gene expression, appears to be involved in the development of schizophrenia (SZ). In this study, we investigated 7562 DNA methylation markers in blood from 98 SZ patients and 108 healthy controls. A linear regression model including age, gender, race, alcohol, nicotine and cannabis use status, and diagnosis was implemented to identify C-phosphate-G (CpG) sites significantly associated with diagnosis. These CpG sites were further validated using an independent data set. Sixteen CpG sites were identified with hyper- or hypomethylation in patients. A further verification of expression of the corresponding genes identified 7 genes whose expression levels were also significantly altered in patients. While such altered methylation patterns showed no correlation with disorganized symptoms and negative symptoms in patients, 11 CpG sites significantly correlated with reality distortion symptoms. The direction of the correlations indicates that methylation changes possibly play a protective mechanism to lessen delusion and hallucination symptoms in patients. Pathway analyses showed that the most significant biological function of the differentially methylated CpGs is inflammatory response with CD224, LAX1, TXK, PRF1, CD7, MPG, and MPO genes directly involved in activations of T cells, B cells, and natural killer cells or in cytotoxic reaction. Our results suggest that such methylation changes may modulate aspects of the immune response and hence protect against the neurobiological substrate of reality distortion symptoms in SZ patients.
Original languageEnglish
Pages (from-to)769-776
Number of pages8
JournalSchizophrenia Bulletin
Volume40
Issue number4
DOIs
Publication statusPublished - Jul 2014

Keywords

  • Adult
  • Alcoholism
  • Case-Control Studies
  • CpG Islands
  • DNA Methylation
  • Epigenesis, Genetic
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Inflammation
  • Linear Models
  • Male
  • Marijuana Abuse
  • Schizophrenia
  • Schizophrenic Psychology
  • Smoking
  • Young Adult

Cite this

Liu, J., Chen, J., Ehrlich, S., Walton, E., White, T., Perrone-Bizzozero, N., ... Calhoun, V. D. (2014). Methylation patterns in whole blood correlate with symptoms in schizophrenia patients. Schizophrenia Bulletin, 40(4), 769-776. https://doi.org/10.1093/schbul/sbt080

Methylation patterns in whole blood correlate with symptoms in schizophrenia patients. / Liu, Jingyu; Chen, Jiayu; Ehrlich, Stefan; Walton, Esther; White, Tonya; Perrone-Bizzozero, Nora; Bustillo, Juan; Turner, Jessica A; Calhoun, Vince D.

In: Schizophrenia Bulletin, Vol. 40, No. 4, 07.2014, p. 769-776.

Research output: Contribution to journalArticle

Liu, J, Chen, J, Ehrlich, S, Walton, E, White, T, Perrone-Bizzozero, N, Bustillo, J, Turner, JA & Calhoun, VD 2014, 'Methylation patterns in whole blood correlate with symptoms in schizophrenia patients', Schizophrenia Bulletin, vol. 40, no. 4, pp. 769-776. https://doi.org/10.1093/schbul/sbt080
Liu, Jingyu ; Chen, Jiayu ; Ehrlich, Stefan ; Walton, Esther ; White, Tonya ; Perrone-Bizzozero, Nora ; Bustillo, Juan ; Turner, Jessica A ; Calhoun, Vince D. / Methylation patterns in whole blood correlate with symptoms in schizophrenia patients. In: Schizophrenia Bulletin. 2014 ; Vol. 40, No. 4. pp. 769-776.
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AU - Turner, Jessica A

AU - Calhoun, Vince D

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N2 - DNA methylation, one of the main epigenetic mechanisms to regulate gene expression, appears to be involved in the development of schizophrenia (SZ). In this study, we investigated 7562 DNA methylation markers in blood from 98 SZ patients and 108 healthy controls. A linear regression model including age, gender, race, alcohol, nicotine and cannabis use status, and diagnosis was implemented to identify C-phosphate-G (CpG) sites significantly associated with diagnosis. These CpG sites were further validated using an independent data set. Sixteen CpG sites were identified with hyper- or hypomethylation in patients. A further verification of expression of the corresponding genes identified 7 genes whose expression levels were also significantly altered in patients. While such altered methylation patterns showed no correlation with disorganized symptoms and negative symptoms in patients, 11 CpG sites significantly correlated with reality distortion symptoms. The direction of the correlations indicates that methylation changes possibly play a protective mechanism to lessen delusion and hallucination symptoms in patients. Pathway analyses showed that the most significant biological function of the differentially methylated CpGs is inflammatory response with CD224, LAX1, TXK, PRF1, CD7, MPG, and MPO genes directly involved in activations of T cells, B cells, and natural killer cells or in cytotoxic reaction. Our results suggest that such methylation changes may modulate aspects of the immune response and hence protect against the neurobiological substrate of reality distortion symptoms in SZ patients.

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