Department of Neuropsychiatry, Faculty of Life Sciences, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Support Center for Women Health Care Professionals and Researchers, Tokyo Women's Medical University, Tokyo, Japan.
Psychiatry Clin Neurosci. 2018 Apr;72(4):245-254. doi: 10.1111/pcn.12645. Epub 2018 Mar 11.
Schizophrenia (SZ) and bipolar disorder (BD) have been known to share genetic and environmental risk factors, and complex gene-environmental interactions may contribute to their pathophysiology. In contrast to high genetic overlap between SZ and BD, as revealed by genome-wide association studies, the extent of epigenetic overlap remains largely unknown. In the present study, we explored whether SZ and BD share epigenetic risk factors in the same manner as they share genetic components.
We performed DNA methylation analyses of the CpG sites in the top five candidate regions (FAM63B, ARHGAP26, CTAGE11P, TBC1D22A, and intergenic region [IR] on chromosome 16) reported in a previous methylome-wide association study (MWAS) of SZ, using whole blood samples from subjects with BD and controls.
Among the five candidate regions, the CpG sites in FAM63B and IR on chromosome 16 were significantly hypomethylated in the samples from subjects with BD as well as those from subjects with SZ. On the other hand, the CpG sites in TBC1D22A were hypermethylated in the samples from subjects with BD, in contrast to hypomethylation in the samples from subjects with SZ.
Hypomethylation of FAM63B and IR on chromosome 16 could be common epigenetic risk factors for SZ and BD. Further comprehensive epigenetic studies for BD, such as MWAS, will uncover the extent of similarity and uniqueness of epigenetic alterations.
精神分裂症（SZ）和双相情感障碍（BD）已知具有遗传和环境风险因素，复杂的基因-环境相互作用可能导致其病理生理学。与全基因组关联研究揭示的 SZ 和 BD 之间存在较高的遗传重叠不同，表观遗传重叠的程度在很大程度上尚不清楚。在本研究中，我们探讨了 SZ 和 BD 是否以与遗传成分相同的方式共享表观遗传风险因素。
我们使用来自 BD 患者和对照的全血样本，对先前 SZ 甲基化全基因组关联研究（MWAS）报告的五个候选区域（FAM63B、ARHGAP26、CTAGE11P、TBC1D22A 和 16 号染色体上的基因间区 [IR]）中的 CpG 位点进行 DNA 甲基化分析。
在五个候选区域中，BD 患者和 SZ 患者样本中的 FAM63B 和 16 号染色体上的 IR 中的 CpG 位点明显低甲基化，而 TBC1D22A 中的 CpG 位点在 BD 患者样本中呈高甲基化，而在 SZ 患者样本中呈低甲基化。
FAM63B 和 16 号染色体上的 IR 低甲基化可能是 SZ 和 BD 的共同表观遗传风险因素。进一步对 BD 进行全基因组表观遗传研究，如 MWAS，将揭示表观遗传改变的相似性和独特性的程度。
