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


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.

SUBMITTER: van den Oord EJ 

PROVIDER: S-EPMC4903046 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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

van den Oord Edwin J C G EJ   Clark Shaunna L SL   Xie Lin Ying LY   Shabalin Andrey A AA   Dozmorov Mikhail G MG   Kumar Gaurav G   Vladimirov Vladimir I VI   Magnusson Patrik K E PK   Aberg Karolina A KA  

Schizophrenia bulletin 20151209 4


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 sampl  ...[more]

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