High Precision DNA Modification Analysis of HCG9 in Major Psychosis

• Published in: Schizophrenia bulletin Vol. 42; no. 1; pp. sbv079 - 177
• Main Authors: Pal, Mrinal, Ebrahimi, Sasha, Oh, Gabriel, Khare, Tarang, Zhang, Aiping, Kaminsky, Zachary A., Wang, Sun-Chong, Petronis, Arturas
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.01.2016
• Subjects: Adult; Aged; Aged, 80 and over; Bipolar Disorder - genetics; Bipolar Disorder - metabolism; Brain - metabolism; Cadaver; Case-Control Studies; DNA - metabolism; DNA Methylation; Epigenesis, Genetic; Female; Humans; Male; Middle Aged; Prefrontal Cortex - metabolism; Psychotic Disorders - genetics; Psychotic Disorders - metabolism; Regular; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Schizophrenia - genetics; Schizophrenia - metabolism; Sequence Analysis, DNA; bipolar disorder; bisulfite sequencing; schizophrenia; brain; epigenetics; padlock probes
• ISSN: 0586-7614; 1745-1701; 1745-1701
• DOI: 10.1093/schbul/sbv079

New epigenetic technologies may uncover etiopathogenic mechanisms of major psychosis. In this study, we applied padlock probe-based ultra-deep bisulfite sequencing for fine mapping of modified cytosines of the HLA complex group 9 (nonprotein coding) gene in the postmortem brains of individuals affected with schizophrenia or bipolar disorder and unaffected controls. Significant differences between patients and controls were detected in both CpG and CpH modifications. In addition, we identified epigenetic age effects, DNA modification differences between sense and anti-sense strands, and demonstrated how DNA modification data can be used in clustering of patient populations. Our findings revealed new epigenetic complexities but also highlighted the potential of DNA modification approaches in the search of heterogeneous causes of major psychiatric disease.