| 1 | JAMA Psychiatry 2014 Mar 71: 255-64 |
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| PMID | 24402055 |
| Title | Methylome-wide association study of schizophrenia: identifying blood biomarker signatures of environmental insults. |
| Abstract | Epigenetic studies present unique opportunities to advance schizophrenia research because they can potentially account for many of its clinical features and suggest novel strategies to improve disease management. To identify schizophrenia DNA methylation biomarkers in blood. The sample consisted of 759 schizophrenia cases and 738 controls (N?=?1497) collected in Sweden. We used methyl-CpG-binding domain protein-enriched genome sequencing of the methylated genomic fraction, followed by next-generation DNA sequencing. We obtained a mean (SD) number of 68 (26.8) million reads per sample. This massive data set was processed using a specifically designed data analysis pipeline. Critical top findings from our methylome-wide association study (MWAS) were replicated in independent case-control participants using targeted pyrosequencing of bisulfite-converted DNA. Status of schizophrenia cases and controls. Our MWAS suggested a considerable number of effects, with 25 sites passing the highly conservative Bonferroni correction and 139 sites significant at a false discovery rate of 0.01. Our top MWAS finding, which was located in FAM63B, replicated with P?=?2.3?×?10-10. It was part of the networks regulated by microRNA that can be linked to neuronal differentiation and dopaminergic gene expression. Many other top MWAS results could be linked to hypoxia and, to a lesser extent, infection, suggesting that a record of pathogenic events may be preserved in the methylome. Our findings also implicated a site in RELN, one of the most frequently studied candidates in methylation studies of schizophrenia. To our knowledge, the present study is one of the first MWASs of disease with a large sample size using a technology that provides good coverage of methylation sites across the genome. Our results demonstrated one of the unique features of methylation studies that can capture signatures of environmental insults in peripheral tissues. Our MWAS suggested testable hypotheses about disease mechanisms and yielded biomarkers that can potentially be used to improve disease management. |
| SCZ Keywords | schizophrenia |
| 2 | Clin Epigenetics 2016 -1 8: 52 |
| PMID | 27175219 |
| Title | Hypomethylation of FAM63B in bipolar disorder patients. |
| Abstract | Bipolar disorder (BD) and schizophrenia (SZ) are known to share common genetic and psychosocial risk factors. A recent epigenome-wide association study performed on blood samples from SZ patients found significant hypomethylation of FAM63B in exon 9. Here, we used iPLEX-based methylation analysis to investigate two CpG sites in FAM63B in blood samples from 459 BD cases and 268 controls. Both sites were significantly hypomethylated in BD cases (lowest p value?=?3.94 × 10(-8)). The methylation levels at the two sites were correlated, and no strong correlation was found with nearby single nucleotide polymorphisms (SNPs), suggesting that methylation differences at these sites are not readably picked up by genome-wide association studies. Overall, FAM63B hypomethylation was found in BD patients, thus replicating the initial finding in SZ patients. This study suggests that FAM63B is a shared epigenetic risk gene for the two disorders. |
| SCZ Keywords | schizophrenia |