Given the difficulty of procuring human brain tissue, a key question in
molecular psychiatry concerns the extent to which epigenetic signatures
measured in more accessible tissues such as blood can serve as a
surrogate marker for the brain. Here, we aimed (1) to investigate the
blood-brain correspondence of DNA methylation using a within-subject
design and (2) to identify changes in DNA methylation of brain-related
biological pathways in schizophrenia.We obtained paired blood and
temporal lobe biopsy samples simultaneously from 12 epilepsy patients
during neurosurgical treatment. Using the Infinium 450K methylation
array we calculated similarity of blood and brain DNA methylation for
each individual separately. We applied our findings by performing gene
set enrichment analyses (GSEA) of peripheral blood DNA methylation data
(Infinium 27K) of 111 schizophrenia patients and 122 healthy controls
and included only Cytosine-phosphate-Guanine (CpG) sites that were
significantly correlated across tissues.Only 7.9% of CpG sites showed a
statistically significant, large correlation between blood and brain
tissue, a proportion that although small was significantly greater than
predicted by chance. GSEA analysis of schizophrenia data revealed
altered methylation profiles in pathways related to precursor
metabolites and signaling peptides.Our findings indicate that most DNA
methylation markers in peripheral blood do not reliably predict brain
DNA methylation status. However, a subset of peripheral data may proxy
methylation status of brain tissue. Restricting the analysis to these
markers can identify meaningful epigenetic differences in schizophrenia
and potentially other brain disorders.
molecular psychiatry concerns the extent to which epigenetic signatures
measured in more accessible tissues such as blood can serve as a
surrogate marker for the brain. Here, we aimed (1) to investigate the
blood-brain correspondence of DNA methylation using a within-subject
design and (2) to identify changes in DNA methylation of brain-related
biological pathways in schizophrenia.We obtained paired blood and
temporal lobe biopsy samples simultaneously from 12 epilepsy patients
during neurosurgical treatment. Using the Infinium 450K methylation
array we calculated similarity of blood and brain DNA methylation for
each individual separately. We applied our findings by performing gene
set enrichment analyses (GSEA) of peripheral blood DNA methylation data
(Infinium 27K) of 111 schizophrenia patients and 122 healthy controls
and included only Cytosine-phosphate-Guanine (CpG) sites that were
significantly correlated across tissues.Only 7.9% of CpG sites showed a
statistically significant, large correlation between blood and brain
tissue, a proportion that although small was significantly greater than
predicted by chance. GSEA analysis of schizophrenia data revealed
altered methylation profiles in pathways related to precursor
metabolites and signaling peptides.Our findings indicate that most DNA
methylation markers in peripheral blood do not reliably predict brain
DNA methylation status. However, a subset of peripheral data may proxy
methylation status of brain tissue. Restricting the analysis to these
markers can identify meaningful epigenetic differences in schizophrenia
and potentially other brain disorders.
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