UNIVERSITY OF ILLINOIS AT CHICAGO Department of Psychiatry Fifth Annual Research Forum – Extravaganza 2014 POSTER TITLE Circadian changes of DNA methylation and gene expression in human blood DISEASE/KEY WORDS: Circadian rhythms, DNA methylation, gene expression, blood AUTHORS: Chunyu Liu1, 3, Jinsong Tang2, Haiyan Tang3, Hua Yun Chen4, Chao Chen3, Yiqiao Hu3, Xiaogang Chen2 1 Department of Psychiatry, University of Illinois at Chicago, Chicago Mental Health Institute, the Second Xiangya Hospital, Central South University, Changsha 3 State Key Laboratory of Medical Genetics, Central South University, Changsha 4 School of Public Health, University of Illinois at Chicago, Chicago RESEARCH MENTOR: 2 MENTEE CATEGORY: BACKGROUND: METHODS: RESULTS: Circadian rhythms have been strongly implicated in mood disorders and other neuropsychiatric disorders. But the actual genes and related regulatory mechanisms remain to be found. In this study, we aim to find out whether DNA methylation is involved in regulating circadian expressions, to prepare for discovering epigenetic biomarkers for related neuropsychiatric disorders. We performed the first genome-wide study of DNA circadian methylation in human blood, along with gene expression. We collected blood DNA at 6 time-points in 24 hours from 8 healthy male individuals. Four of the individuals also provided RNA samples from whole blood. Illumina Infinium HumanMethylation450 and HumanHT12 Expression BeadChip were used to measure genome-wide DNA methylation and gene expression respectively. After filtering and preprocessing, we assessed DNA methylation levels at 275,337 CpG sites, and gene expression of 15,519 genes. By fitting to a sine curve with a period length of 24 hours, we detected 408 CpG sites that have epigenome-wide significant (P < 1.82e-7, Bonferroni correction threshold) fit to the circadian pattern of methylation variation. We also detected 66 genes that have genome-wide significant (P < 3.22e-6, Bonferroni correction threshold) fit to the circadian pattern. Two genes with circadian cycling expression, PLEKHO2 and PRDM1, also have nearby CpG sites showing significant cycling methylation. Their expression and methylation showed modest correlation, as well. UNIVERSITY OF ILLINOIS AT CHICAGO Department of Psychiatry CONCLUSIONS: These data suggest that DNA methylation may play a modest role in regulating circadian rhythms, and they could be used to prioritize candidates for finding the biomarkers for mood disorders.