Correlation between DNA methylation and gene expression in the brains of patients with bipolar disorder and schizophrenia

Chao Chen, Chunling Zhang, Lijun Cheng, James L. Reilly, Jeffrey R. Bishop, John A. Sweeney, Hua Yun Chen, Elliot S. Gershon, Chunyu Liu

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Objectives: Aberrant DNA methylation and gene expression have been reported in postmortem brain tissues of psychotic patients, but until now there has been no systematic evaluation of synergistic changes in methylation and expression on a genome-wide scale in brain tissue. Methods: In this study, genome-wide methylation and expression analyses were performed on cerebellum samples from 39 patients with schizophrenia, 36 patients with bipolar disorder, and 43 unaffected controls, to screen for a correlation between gene expression and CpG methylation. Results: Out of 71,753 CpG gene pairs (CGPs) tested across the genome, 204 were found to significantly correlate with gene expression after correction for multiple testing [p < 0.05, false discovery rate (FDR) q < 0.05]. The correlated CGPs were tested for disease-associated expression and methylation by comparing psychotic patients with bipolar disorder and schizophrenia to healthy controls. Four of the identified CGPs were found to significantly correlate with the differential expression and methylation of genes encoding phosphoinositide-3-kinase, regulatory subunit 1 (PIK3R1), butyrophilin, subfamily 3, member A3 (BTN3A3), nescient helix-loop-helix 1 (NHLH1), and solute carrier family 16, member 7 (SLC16A7) in psychotic patients (p < 0.05, FDR q < 0.2). Additional expression and methylation datasets were used to validate the relationship between DNA methylation, gene expression, and neuropsychiatric diseases. Conclusions: These results suggest that the identified differentially expressed genes with an aberrant methylation pattern may represent novel candidate factors in the etiology and pathology of neuropsychiatric disorders.

Original languageEnglish (US)
Pages (from-to)790-799
Number of pages10
JournalBipolar Disorders
Volume16
Issue number8
DOIs
StatePublished - Dec 1 2014

Fingerprint

DNA Methylation
Bipolar Disorder
Methylation
Schizophrenia
Gene Expression
Brain
Genome
Class Ia Phosphatidylinositol 3-Kinase
Genes
Cerebellum
Pathology

Keywords

  • Bipolar disorder
  • Butyrophilin, subfamily 3, member A3 (BTN3A3)
  • CpG gene pairs (CGPs)
  • DNA methylation
  • Gene expression
  • Nescient helix-loop-helix 1 (NHLH1)
  • Phosphoinositide-3-kinase, regulatory subunit 1 (PIK3R1)
  • Schizophrenia
  • Solute carrier family 16, member 7 (SLC16A7)

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Chen, C., Zhang, C., Cheng, L., Reilly, J. L., Bishop, J. R., Sweeney, J. A., ... Liu, C. (2014). Correlation between DNA methylation and gene expression in the brains of patients with bipolar disorder and schizophrenia. Bipolar Disorders, 16(8), 790-799. https://doi.org/10.1111/bdi.12255

Correlation between DNA methylation and gene expression in the brains of patients with bipolar disorder and schizophrenia. / Chen, Chao; Zhang, Chunling; Cheng, Lijun; Reilly, James L.; Bishop, Jeffrey R.; Sweeney, John A.; Chen, Hua Yun; Gershon, Elliot S.; Liu, Chunyu.

In: Bipolar Disorders, Vol. 16, No. 8, 01.12.2014, p. 790-799.

Research output: Contribution to journalArticle

Chen, C, Zhang, C, Cheng, L, Reilly, JL, Bishop, JR, Sweeney, JA, Chen, HY, Gershon, ES & Liu, C 2014, 'Correlation between DNA methylation and gene expression in the brains of patients with bipolar disorder and schizophrenia', Bipolar Disorders, vol. 16, no. 8, pp. 790-799. https://doi.org/10.1111/bdi.12255
Chen, Chao ; Zhang, Chunling ; Cheng, Lijun ; Reilly, James L. ; Bishop, Jeffrey R. ; Sweeney, John A. ; Chen, Hua Yun ; Gershon, Elliot S. ; Liu, Chunyu. / Correlation between DNA methylation and gene expression in the brains of patients with bipolar disorder and schizophrenia. In: Bipolar Disorders. 2014 ; Vol. 16, No. 8. pp. 790-799.
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abstract = "Objectives: Aberrant DNA methylation and gene expression have been reported in postmortem brain tissues of psychotic patients, but until now there has been no systematic evaluation of synergistic changes in methylation and expression on a genome-wide scale in brain tissue. Methods: In this study, genome-wide methylation and expression analyses were performed on cerebellum samples from 39 patients with schizophrenia, 36 patients with bipolar disorder, and 43 unaffected controls, to screen for a correlation between gene expression and CpG methylation. Results: Out of 71,753 CpG gene pairs (CGPs) tested across the genome, 204 were found to significantly correlate with gene expression after correction for multiple testing [p < 0.05, false discovery rate (FDR) q < 0.05]. The correlated CGPs were tested for disease-associated expression and methylation by comparing psychotic patients with bipolar disorder and schizophrenia to healthy controls. Four of the identified CGPs were found to significantly correlate with the differential expression and methylation of genes encoding phosphoinositide-3-kinase, regulatory subunit 1 (PIK3R1), butyrophilin, subfamily 3, member A3 (BTN3A3), nescient helix-loop-helix 1 (NHLH1), and solute carrier family 16, member 7 (SLC16A7) in psychotic patients (p < 0.05, FDR q < 0.2). Additional expression and methylation datasets were used to validate the relationship between DNA methylation, gene expression, and neuropsychiatric diseases. Conclusions: These results suggest that the identified differentially expressed genes with an aberrant methylation pattern may represent novel candidate factors in the etiology and pathology of neuropsychiatric disorders.",
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AU - Zhang, Chunling

AU - Cheng, Lijun

AU - Reilly, James L.

AU - Bishop, Jeffrey R.

AU - Sweeney, John A.

AU - Chen, Hua Yun

AU - Gershon, Elliot S.

AU - Liu, Chunyu

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N2 - Objectives: Aberrant DNA methylation and gene expression have been reported in postmortem brain tissues of psychotic patients, but until now there has been no systematic evaluation of synergistic changes in methylation and expression on a genome-wide scale in brain tissue. Methods: In this study, genome-wide methylation and expression analyses were performed on cerebellum samples from 39 patients with schizophrenia, 36 patients with bipolar disorder, and 43 unaffected controls, to screen for a correlation between gene expression and CpG methylation. Results: Out of 71,753 CpG gene pairs (CGPs) tested across the genome, 204 were found to significantly correlate with gene expression after correction for multiple testing [p < 0.05, false discovery rate (FDR) q < 0.05]. The correlated CGPs were tested for disease-associated expression and methylation by comparing psychotic patients with bipolar disorder and schizophrenia to healthy controls. Four of the identified CGPs were found to significantly correlate with the differential expression and methylation of genes encoding phosphoinositide-3-kinase, regulatory subunit 1 (PIK3R1), butyrophilin, subfamily 3, member A3 (BTN3A3), nescient helix-loop-helix 1 (NHLH1), and solute carrier family 16, member 7 (SLC16A7) in psychotic patients (p < 0.05, FDR q < 0.2). Additional expression and methylation datasets were used to validate the relationship between DNA methylation, gene expression, and neuropsychiatric diseases. Conclusions: These results suggest that the identified differentially expressed genes with an aberrant methylation pattern may represent novel candidate factors in the etiology and pathology of neuropsychiatric disorders.

AB - Objectives: Aberrant DNA methylation and gene expression have been reported in postmortem brain tissues of psychotic patients, but until now there has been no systematic evaluation of synergistic changes in methylation and expression on a genome-wide scale in brain tissue. Methods: In this study, genome-wide methylation and expression analyses were performed on cerebellum samples from 39 patients with schizophrenia, 36 patients with bipolar disorder, and 43 unaffected controls, to screen for a correlation between gene expression and CpG methylation. Results: Out of 71,753 CpG gene pairs (CGPs) tested across the genome, 204 were found to significantly correlate with gene expression after correction for multiple testing [p < 0.05, false discovery rate (FDR) q < 0.05]. The correlated CGPs were tested for disease-associated expression and methylation by comparing psychotic patients with bipolar disorder and schizophrenia to healthy controls. Four of the identified CGPs were found to significantly correlate with the differential expression and methylation of genes encoding phosphoinositide-3-kinase, regulatory subunit 1 (PIK3R1), butyrophilin, subfamily 3, member A3 (BTN3A3), nescient helix-loop-helix 1 (NHLH1), and solute carrier family 16, member 7 (SLC16A7) in psychotic patients (p < 0.05, FDR q < 0.2). Additional expression and methylation datasets were used to validate the relationship between DNA methylation, gene expression, and neuropsychiatric diseases. Conclusions: These results suggest that the identified differentially expressed genes with an aberrant methylation pattern may represent novel candidate factors in the etiology and pathology of neuropsychiatric disorders.

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KW - Phosphoinositide-3-kinase, regulatory subunit 1 (PIK3R1)

KW - Schizophrenia

KW - Solute carrier family 16, member 7 (SLC16A7)

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