Cited by 47Epigenetics and DNA MethylationSchizophrenia research and treatmentGenetic Associations and Epidemiology

A Whole Methylome CpG-SNP Association Study of Psychosis in Blood and Brain Tissue

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van den Oord, Edwin J. C. G., Clark, Shaunna L., Xie, Lin Ying, Shabalin, Andrey A., Dozmorov, Mikhail G., Kumar, Gaurav, Swedish Schizophrenia Consortium, Vladimirov, Vladimir I. +2 more·2016·Schizophrenia Bulletin

Abstract

Mutated CpG sites (CpG-SNPs) are potential hotspots for human diseases because in addition to the sequence variation they may show individual differences in DNA methylation. We performed methylome-wide association studies (MWAS) to test whether methylation differences at those sites were associated with schizophrenia. We assayed all common CpG-SNPs with methyl-CpG binding domain protein-enriched genome sequencing (MBD-seq) using DNA extracted from 1408 blood samples and 66 postmortem brain samples (BA10) of schizophrenia cases and controls. Seven CpG-SNPs passed our FDR threshold of 0.1 in the blood MWAS. Of the CpG-SNPs methylated in brain, 94% were also methylated in blood. This significantly exceeded the 46.2% overlap expected by chance (P-value < 1.0×10(-8)) and justified replicating findings from blood in brain tissue. CpG-SNP rs3796293 in IL1RAP replicated (P-value = .003) with the same direction of effects. This site was further validated through targeted bisulfite pyrosequencing in 736 independent case-control blood samples (P-value < 9.5×10(-4)). Our top result in the brain MWAS (P-value = 8.8×10(-7)) was CpG-SNP rs16872141 located in the potential promoter of ENC1. Overall, our results suggested that CpG-SNP methylation may reflect effects of environmental insults and can provide biomarkers in blood that could potentially improve disease management.

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Crossref · 10.1093/schbul/sbv182

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  • It is known that schizophrenia patients have upregulated genes for inflammatory cytokines, and downregulated Bdnf gene transcription.

    “It is known that schizophrenia patients have upregulated genes for inflammatory cytokines [122, 123], and downregulated Bdnf gene transcription [124, 125].”

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Authors
van den Oord, E. J. C. G., Clark, S. L., Xie, L. Y., Shabalin, A. A., Dozmorov, M. G., Kumar, G., Swedish Schizophrenia Consortium, Vladimirov, V. I., Magnusson, P. K. E., & Aberg, K. A.
Affiliations
  • Virginia Commonwealth University (US)
  • Johns Hopkins University (US)
  • Karolinska Institutet (SE)
Venue
Schizophrenia Bulletin
Published
2015-12-09
Volume
42
Issue
4
Pages
1018-1026
ISSN
  • 0586-7614 (ISSN-L)
  • 1745-1701
OpenAlex
W2283549005
Cited by
47
References
69
Citations by year
2026: 1 · 2025: 5 · 2023: 1 · 2022: 6 · 2021: 5 · 2020: 10 · 2019: 4 · 2018: 8 · 2017: 3 · 2016: 4
FWCI
2.17
Type
journal article
Language
en
Open access
Locations
  • Schizophrenia Bulletin (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
  • Stanley Medical Research Institute
  • Translational Genomics Research Institute
  • National Institute on Alcohol Abuse and Alcoholism (K01AA021266)
  • National Institute of Mental Health (R03MH102723, R01MH097283, RC2MH089996)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords
schizophrenia, DNA methylation
MeSH terms
Adult, Aged, Autopsy, Brain, Female, Humans, Male, Microfilament Proteins, Middle Aged, Neuropeptides, Nuclear Proteins, Psychotic Disorders, Schizophrenia, Biomarkers, Case-Control Studies, CpG Islands, DNA Methylation, Polymorphism, Single Nucleotide, Genome-Wide Association Study

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