A whole methylome CpG-SNP association study of psychosis in blood and brain tissue

Swedish Schizophrenia Consortium

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)


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 CpGSNPs 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 CpGSNPs 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.

Original languageEnglish
Pages (from-to)1018-1026
Number of pages9
JournalSchizophrenia Bulletin
Issue number4
Publication statusPublished - 2016
Externally publishedYes


  • DNA methylation
  • MBD-seq
  • methylome-wide association study
  • postmortem brain samples
  • SNPs


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