Genetics and Epigenetics of Psychiatric Disorders

Epigenetics;psychiatric disorders;Human Genetics and Molecular Biology

Shu, ChangJi, Hongkai ;

Johns Hopkins University

关键词: Epigenetics;    psychiatric disorders;    Human Genetics and Molecular Biology;   

Others  :  https://jscholarship.library.jhu.edu/bitstream/handle/1774.2/61033/SHU-DISSERTATION-2018.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: JOHNS HOPKINS DSpace Repository

【 摘 要 】

Genetics and epigenetics studies have been used widely for psychiatric and behavior disorders such as substance use and Autism Spectrum Disorders(ASD). By utilizing genetics on ASD and epigenetics data on injection drug use(IDU) from the Department of Mental Health, we are able to identify genetic or epigenetic region of interests. In Aim 1 and Aim 2, we used an ongoing longitudinal data called the AIDS Linked to the Intravenous Experience (ALIVE) study, and it contained past six month IDU phenotypic data and epigenetics data from peripheral blood on 2-4 visits from 288 subjects. Taking advantage of the longitudinal design, we conducted four separate epigenome-wide association analyses(EWAS) on past six month any injection drug use, heroin only injection use, cocaine only injection use, and co-use of heroin and cocaine injection. To borrow information across these four separate EWASs based on correlated phenotypes, we modified the correlation motif method and applied it into epigenetics data, and the top hits after joint analyses by correlation motif are now epigenome-wide significant after adjusting for multiple comparison. The epigenetic marker near the FKBP5 gene was found to be associated with IDU, which is also a gene of interest for other types of psychiatric disorders. In the ALIVE study, we also conducted EWAS on HIV, and used PCs that are negatively associated with CD4+ cells and positively associated with CD8+ cells to account for cell composition difference between chronic HIV infected individuals and HIV negative individuals. We discovered a epigenome-wide significant methylation site near NLRC5 gene, which is also reported in an independent EWAS study on HIV. In another genetic study called the Study to Explore Early Development (SEED), we have ASD phenotypic information and genetics information on about 1200 cases and controls. We utilized brain expression quantitative loci(brain eQTLs) from public literature to extract brain eQTL single nucleotide polymorphism(brain eSNPs) to reduce the search space from genome-wide variation to only brain expression related SNPs. We discovered that only temporal cortex eSNPs shows qqplots that is of suggestive association, and other brain region eSNPs are significantly deflated. This finding confirms with other imaging studies on temporal cortex might be affected by ASD.