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- Title
Exploring the relationship of DNA sequence and methylation within the NDUFA13/YJEFN3 genes with cognitive deficits in schizophrenia.
- Authors
Alfimova, M.; Kondratyev, N.; Golov, A.; Lezheiko, T.; Golimbet, V.
- Abstract
Introduction: Epigenetic marks may potentially serve as biomarkers of psychiatric disorders that guide the development of targeted therapies. Objectives: In the search for epigenetic markers of cognitive deficits in schizophrenia, we investigated DNA methylation of a genomic region in 19p13.11 associated with schizophrenia in both the largest genetic and epigenetic genome-wide association studies. Methods: A DNA fragment within the NDUFA13/YJEFN3 genes (hg19 chr19:19642955-19643856) was analyzed in blood of 70 schizophrenia patients and 72 controls with single molecule real-time bisulfite sequencing. Methylation at 43 individual CpGs and averaged methylation of functionally different fragments such as the introns, CpG island and exon were analyzed for the associations with the schizophrenia risk haplotype ATG (rs10422819-rs113527843-rs8100927) and a composite cognitive score. Results: Controlling for demographic variables, coverage and haplotype, we did not find any significant difference in methylation between patients and controls. In the entire sample, the significant and nominally significant (p<0.01) allele-specific methylation (ASM) was found at the CpG-SNP rs10422819 and a nearby CpG (cg08623644), respectively. Moreover, the methylation level at cg08623644 predicted the cognitive score, while the haplotype had no influence on cognition. A further analysis confirmed ASM but not the relationship between methylation at cg08623644 and cognition in the controls. In contrast, in the patient group, methylation at cg08623644 did not demonstrate ASM but negatively correlated with the cognitive score. Conclusions: The results suggest themethylation level at cg08623644 might reflect a pathological process associated with the development of cognitive deficits in schizophrenia. This work was supported by the Russian Scientific Foundation, grant 16-15-00056.
- Subjects
DNA methylation; EPIGENOMICS; NUCLEOTIDE sequence; DNA sequencing; GENOME-wide association studies; SCHIZOPHRENIA
- Publication
European Psychiatry, 2020, Vol 63, pS407
- ISSN
0924-9338
- Publication type
Article