Hiroko Sugawara1,2, Yui Murata3, Tempei Ikegame4, Rie Sawamura3, Shota Shimanaga3, Yusuke Takeoka3, Takeo Saito5, Masashi Ikeda5, Akane Yoshikawa4, Fumichika Nishimura4, Yoshiya Kawamura6, Chihiro Kakiuchi4, Tsukasa Sasaki7, Nakao Iwata5, Mamoru Hashimoto1, Kiyoto Kasai4, Tadafumi Kato8, Miki Bundo3,9, Kazuya Iwamoto3. 1. Department of Neuropsychiatry, Faculty of Life Sciences, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. 2. Support Center for Women Health Care Professionals and Researchers, Tokyo Women's Medical University, Tokyo, Japan. 3. Department of Molecular Brain Science, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. 4. Department of Neuropsychiatry, The University of Tokyo, Tokyo, Japan. 5. Department of Psychiatry, Fujita Health University School of Medicine, Aichi, Japan. 6. Department of Psychiatry, Shonan Kamakura General Hospital, Kamakura, Japan. 7. Laboratory of Health Education, Graduate School of Education, The University of Tokyo, Tokyo, Japan. 8. Laboratory for Molecular Dynamics of Mental Disorders, RIKEN Brain Science Institute, Saitama, Japan. 9. PRESTO, Japan Science and Technology Agency, Tokyo, Japan.
Abstract
AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Authors: Sonia Hesam-Shariati; Bronwyn J Overs; Gloria Roberts; Claudio Toma; Oliver J Watkeys; Melissa J Green; Kerrie D Pierce; Howard J Edenberg; Holly C Wilcox; Emma K Stapp; Melvin G McInnis; Leslie A Hulvershorn; John I Nurnberger; Peter R Schofield; Philip B Mitchell; Janice M Fullerton Journal: Transl Psychiatry Date: 2022-08-03 Impact factor: 7.989