Whole-exome sequencing in three families with affected siblings

• Project/Area Number: 25461724
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Niigata University
• Principal Investigator: Watanabe Yuichiro 新潟大学, 医歯学総合病院, 特任教授 (90401744)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2013: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 統合失調症

Outline of Final Research Achievements

To investigate the role of rare inherited variations, we performed whole-exome sequencing (WES) in three families, each with two affected siblings. We also performed a three-stage follow-up case-control study in a Japanese population with a total of 2617 patients and 2396 controls. WES identified 15 rare truncating variations that were variously present in the two affected siblings in each family. In the follow-up study, four variations (NWD1 W169X, LCORL R7fsX53, CAMK2B L497fsX497, and C9orf89 Q102X) had a higher mutant allele frequency in patients compared with controls, although these associations were not significant in the combined population, which comprised the first-, second- and third-stage populations. These results do not support a contribution of the rare truncating variations identified in the three families to the genetic etiology of schizophrenia.

Research Products

• [Journal Article] Rare truncating variations and risk of schizophrenia: Whole-exome sequencing in three families with affected siblings and a three-stage follow-up study in a Japanese population. (2016)
  • Author(s): Watanabe Y, Nunokawa A, Shibuya M, Ikeda M, Hishimoto A, Kondo K, Egawa J, Kaneko N, Muratake T, Saito T, Okazaki S, Shimasaki A, Igeta H, Inoue E, Hoya S, Sugai T, Sora I, Iwata N, Someya T
  • Journal Title: Psychiatry Research Volume: 235 Pages: 13-18
  • DOI: 10.1016/j.psychres.2015.12.011
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] 統合失調症の分子病態 (2014)
  • Author(s): 渡部雄一郎
  • Journal Title: 新潟医学会雑誌 Volume: 128 Pages: 7-12
  • NAID: 120006758880
• [Journal Article] 統合失調症の分子病態解明を目指して (2014)
  • Author(s): 渡部雄一郎
  • Journal Title: 新潟県医師会報 Volume: 776 Pages: 2-7
• [Journal Article] A rare MIR138-2 gene variation is associated with schizophrenia in a Japanese population (2014)
  • Author(s): Watanabe, Y., Hishimoto, A., Shibuya, M., Nunokawa, A., Kaneko, N., Igeta, Egawa, J., Mouri, K., Sora, I., Someya, T.
  • Journal Title: Psychiatry Research Volume: 215 Issue: 3 Pages: 801-802
  • DOI: 10.1016/j.psychres.2013.12.029
  • Peer Reviewed
• [Journal Article] The cardiomyopathy-associated 5 (CMYA5) gene and risk of schizophrenia: Meta-analysis of rs3828611 and rs4704591 in East Asian populations (2014)
  • Author(s): Watanabe, Y., Shibuya, M., Someya, T.
  • Journal Title: Asian Journal of Psychiatry Volume: ７ Pages: 95-96
  • DOI: 10.1016/j.ajp.2013.10.013
  • Peer Reviewed
• [Journal Article] Interleukin 1 beta gene and risk of schizophrenia : detailed case-control and family-based studies and an updated meta-analysis (2014)
  • Author(s): Shibuya, M., Watanabe, Y., Nunokawa, A., Egawa, J., Kaneko, N., Igeta, H., Someya, T.
  • Journal Title: Human Psychopharmacology : Clinical and Experimental Volume: 29 Issue: 1 Pages: 31-37
  • DOI: 10.1002/hup.2365
  • Peer Reviewed
• [Journal Article] A missense mutation in the ITGA8 gene, a cell adhesion molecule gene, is associated with schizophrenia in Japanese female patients. (2013)
  • Author(s): Supriyanto I, Watanabe Y, Mouri K, Shiroiwa K, Ratta-Apha W, Yoshida M, Tamiya G, Sasada T, Eguchi N, Okazaki K, Shirakawa O, Someya T, Hishimoto A.
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry Volume: 40 Pages: 347-52
  • DOI: 10.1016/j.pnpbp.2012.11.002
  • Peer Reviewed
• [Journal Article] An evaluation of association between a novel hippocampal biology related SNP (rs7294919) and schizophrenia (2013)
  • Author(s): Liu, J., Numata, S., Ikeda, M., Watanabe, Y., Zheng, X., Luo, X., Kinoshita, M., Nunokawa, A., Someya, T., Ohmori, T., Bei, J., Chong, S., Lee, J., Li, Z., Liu, J., Iwata, N., Shi, Y., Li, M., Su, B
  • Journal Title: PLoS One Volume: 8 Issue: 11 Pages: e80696-e80696
  • DOI: 10.1371/journal.pone.0080696
  • Peer Reviewed
• [Journal Article] Replication in a Japanese population that a MIR30E gene variation is associated with schizophrenia (2013)
  • Author(s): Watanabe, Y., Iijima, Y., Egawa, J., Nunokawa, A., Kaneko, N., Arinami, T., Ujike, H., Inada, T., Iwata, N., Kunugi, H., Itokawa, M., Sasaki, T., Ozaki, N., Hashimoto, R., Shibuya, M., Igeta, H., Someya, T.
  • Journal Title: Schizophrenia Research Volume: 150 Issue: 2-3 Pages: 596-597
  • DOI: 10.1016/j.schres.2013.08.028
  • Peer Reviewed
• [Journal Article] An association analysis of the cardiomyopathy-associated 5 (CMYA5) genewith schizophrenia in a Japanese population. (2013)
  • Author(s): Furukawa M, Tochigi M, Otowa T, Arinami T, Inada T, Ujike H, Watanabe Y, Iwata N, Itokawa M, Kunugi H, Hashimoto R, Ozaki N, Kakiuchi C, Kasai K, Sasaki T
  • Journal Title: Psychiatr Genet. Volume: 23(4) Issue: 4 Pages: 179-180
  • DOI: 10.1097/ypg.0b013e328360c8be
  • Peer Reviewed
• [Journal Article] Genetic evidence for association between NOTCH4 and schizophrenia supported by a GWAS follow-up study in a Japanese population (2013)
  • Author(s): Ikeda M, Aleksic B, Yamada K, Iwayama-Shigeno Y, Matsuo K, Numata S, Watanabe Y, Ohnuma T, Kaneko T, Fukuo Y, Okochi T, Toyota T, Hattori E, Shimodera S, Itakura M, Nunokawa A, Shibata N, Tanaka H, Yoneda H, Arai H, Someya T, Ohmori T, Yoshikawa T, Ozaki N, Iwata N
  • Journal Title: Mol Psychiatry Volume: 18(6) Issue: 6 Pages: 636-638
  • DOI: 10.1038/mp.2012.74
  • Peer Reviewed
• [Journal Article] Resequencing and association analysis of MIR137 with schizophrenia in a Japanese population (2013)
  • Author(s): Egawa, J., Nunokawa, A., Shibuya, M., Watanabe, Y., Kaneko, N., Igeta, H., Someya, T.
  • Journal Title: Psychiatry and Clinical Neurosciences Volume: 67 Issue: 4 Pages: 277-279
  • DOI: 10.1111/pcn.12047
  • Peer Reviewed
• [Presentation] マイクロRNA30E遺伝子の稀な変異と統合失調症との関連 (2014)
  • Author(s): 江川純, 飯嶋良味, 渡部雄一郎, 布川綾子, 金子尚史, 有波忠雄, 氏家寛, 稲田俊也, 岩田仲生, 功刀浩, 糸川昌成, 佐々木司, 尾崎紀夫, 橋本亮太, 澁谷雅子, 井桁裕文, 染矢俊幸
  • Organizer: 第36回日本生物学的精神医学会
  • Place of Presentation: 奈良県文化会館（奈良市）
  • Year and Date: 2014-10-01
• [Presentation] マイクロRNA138-2遺伝子の稀な変異と統合失調症との関連 (2014)
  • Author(s): 渡部雄一郎, 菱本明豊, 澁谷雅子,布川綾子, 金子尚史, 井桁裕文, 江川純, 毛利健太朗, 曽良一郎, 染矢俊幸
  • Organizer: 第36回日本生物学的精神医学会
  • Place of Presentation: 奈良県文化会館（奈良市）
  • Year and Date: 2014-09-30
• [Presentation] マイクロRNA137遺伝子のリシーケンスおよび統合失調症との関連解析 (2014)
  • Author(s): 井上絵美子, 江川純, 布川綾子, 澁谷雅子, 渡部雄一郎, 金子尚史, 井桁裕文, 染矢俊幸
  • Organizer: 第36回日本生物学的精神医学会
  • Place of Presentation: 奈良県文化会館（奈良市）
  • Year and Date: 2014-09-30
• [Presentation] TPH2遺伝子と日本人統合失調症との2段階関連解析 (2014)
  • Author(s): 布川綾子, 渡部雄一郎, 飯嶋良味, 江川純, 金子尚史, 澁谷雅子, 有波忠雄, 氏家寛, 稲田俊也, 岩田仲生, 栃木衛, 功刀浩, 糸川昌成, 尾崎紀夫, 橋本亮太, 染矢俊幸
  • Organizer: 第36回日本生物学的精神医学会
  • Place of Presentation: 奈良県文化会館（奈良市）
  • Year and Date: 2014-09-29
• [Presentation] Case-control association study between the tryptophan hydroxylase 2 (TPH2) gene and schizophrenia in a Japanese population (2013)
  • Author(s): Nunokawa A, Watanabe Y, Egawa J, Kaneko N, Shibuya M, Someya T
  • Organizer: 11th World Congress of Biological Psychiatry
  • Place of Presentation: 京都国際会館（京都）
• [Presentation] Measurement and comparison of serum neuregulin 1 immunoreactivity in control subjects and patients with schizophrenia: an influence of its genetic polymorphism (2013)
  • Author(s): Shibuya M, Komi E, Wang R, Kato T, Watanabe Y, Sakai M, Ozaki M, Someya T, Nawa H
  • Organizer: 11th World Congress of Biological Psychiatry
  • Place of Presentation: 京都国際会館（京都）
• [Presentation] Supportive evidence for the association between the Gln2Pro polymorphism in the sigma non-opioid intracellular receptor 1 gene and schizophrenia in the Japanese population (2013)
  • Author(s): Watanabe Y, Nunokawa A, Kaneko N, Shibuya M, Egawa J, Someya T
  • Organizer: 11th World Congress of Biological Psychiatry
  • Place of Presentation: 京都国際会館（京都）