Identification of Parkinson's disease genes and development of the personalized medicine

• Project/Area Number: 25713015
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Human genetics
• Research Institution: Kobe University
• Principal Investigator: SATAKE Wataru 神戸大学, 医学(系)研究科(研究院), 助教 (50467594)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥24,570,000 (Direct Cost: ¥18,900,000、Indirect Cost: ¥5,670,000); Fiscal Year 2015: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2014: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2013: ¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
• Keywords: 神経遺伝 / パーキンソン病 / エクソーム / 個別化医療 / 孤発性神経疾患 / 神経内科学 / 人類遺伝学 / ゲノム医科学

Outline of Final Research Achievements

We performed a genome-wide association study (GWAS) of Parkinson's disease and reported four PD-risk genes previously. Here we performed a large scale exome-association study to identify rare variants with stronger effect size for the disease. We successfully identified fifteen nonsynonymous risk variants for Parkinson's disease.

Research Products

• [Journal Article] Evaluation of the interaction between LRRK2 and PARK16 loci in determining risk of Parkinson's disease: analysis of a large multicenter study. (2017)
  • Author(s): Wang L, Heckman MG, Aasly JO,.., Satake W,.., Farrer MJ, Ross OA, Sharma M
  • Journal Title: Neurobiol Aging. Volume: 49 Pages: 217.e1-217.e4
  • DOI: 10.1016/j.neurobiolaging.2016.09.022
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A novel PIGN mutation and prenatal diagnosis of inherited glycosylphosphatidylinositol deficiency. (2015)
  • Author(s): Nakagawa T, Taniguchi-Ikeda M, Murakami Y, Nakamura S, Motooka D, Emoto T, Satake W, Nishiyama M, Toyoshima D, Morisada N, Takada S, Tairaku S, Okamoto N, Morioka I, Kurahashi H, Toda T, Kinoshita T, Iijima K.
  • Journal Title: American Journal of Medical Genetics PartA Volume: 170 Issue: 1 Pages: 183-188
  • DOI: 10.1002/ajmg.a.37397
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] ABCG2 variant has opposing effects on onset ages of Parkinson's disease and gout. (2015)
  • Author(s): Matsuo H, Tomiyama H, Satake W, Chiba T, Onoue H, Kawamura Y, Nakayama A, ShimizuS, Sakiyama M, Funayama M, Nishioka K, Shimizu T, Kaida K, Kamakura K, Toda T, Hattori N, ShinomiyaN.
  • Journal Title: Ann Clin Transl Neurol Volume: 2 Issue: 3 Pages: 302-306
  • DOI: 10.1002/acn3.167
  • Peer Reviewed / Open Access
• [Journal Article] Variants associated with Gaucher disease in multiple system atrophy. (2015)
  • Author(s): Mitsui J, Matsukawa T, Sasaki H, Yabe I, Nakahara Y, Momose Y, Takahashi Y, Hara K, Kakita A, Yamada M, Takahashi H, Onodera O, Nishizawa M, Watanabe H, Nakashima K, Ito H, Izumi Y, Kaji R, Kato T, Tsuji S, et al.
  • Journal Title: Ann Clin Transl Neurol. Volume: 2 Issue: 4 Pages: 417-426
  • DOI: 10.1002/acn3.185
  • Peer Reviewed / Open Access
• [Journal Article] CHCHD2 mutations in autosomal dominant late-onset Parkinson’s disease: a genome-wide linkage and sequencing study. (2015)
  • Author(s): Funayama M, Ohe K, Amo T, Furuya N, Yamaguchi J, Saiki S, Yuanzhe L, Ogaki K, Ando M, Yoshinon H, Tomiyama H, Nishioka K, Hasegawa K, Saiki H, Satake W, Mogushi K, Sasaki R, Kokubo Y, Kuzuhara S, Toda T, Mizuno Y, Uchiyama Y, Ohno K, Hattori N.
  • Journal Title: Lancet Neurol Volume: 14 Issue: 3 Pages: 274-282
  • DOI: 10.1016/s1474-4422(14)70266-2
  • Peer Reviewed / Open Access
• [Journal Article] The first nationwide survey and genetic analyses of Bardet-Biedl syndrome in Japan (2015)
  • Author(s): Hirano M, Satake W, Ihara K, Tsug I, Kondo S, Saida K, Betsui H, Okubo K, Sakamoto H, Ueno S, Ikuno Y, Ishihara R, Iwahashi H, Ohishi M, Mano T, Yamashita T, Suzuki Y, Nakamura Y, Kusunoki S, Toda T
  • Journal Title: PLOS ONE Volume: 10 Issue: 9 Pages: e0136317-e0136317
  • DOI: 10.1371/journal.pone.0136317
  • Peer Reviewed / Open Access
• [Journal Article] Exome Analyses of Long QT Syndrome Reveal Candidate Pathogenic Mutations in Calmodulin-Interacting Genes. (2015)
  • Author(s): Shigemizu D, Aiba T, Nakagawa H, Ozaki K, Miya F, Satake W, Toda T, Miyamoto Y, Fujimoto A, Suzuki Y, Kubo M, Tsunoda T, Shimizu W, Tanaka T.
  • Journal Title: PLoS One. Volume: 10 (7) Issue: 7 Pages: e0130329-e0130329
  • DOI: 10.1371/journal.pone.0130329
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A de novo mutation of the MYH7 gene in a large Chinese family with autosomal dominant myopathy (2015)
  • Author(s): Oda T, Xiong H, Kobayashi K, Wang S, Satake W, Jiao H, Yang Y, Cha PC, Hayashi Y, Nishino I, Suzuki Y, Sugano S, Wu X, Toda T.
  • Journal Title: Human Genome Variation Volume: 2 Issue: 1 Pages: 15022-15022
  • DOI: 10.1038/hgv.2015.22
  • Peer Reviewed / Open Access
• [Journal Article] Novel calmodulin mutations associated with congenital arrhythmia susceptibility. (2014)
  • Author(s): Makita N, Tsuji Y（39人中21番目）et al
  • Journal Title: Circ Cardiovasc Genet. Volume: 7 Issue: 4 Pages: 466-474
  • DOI: 10.1161/circgenetics.113.000459
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A case of Bardet-Biedl syndrome complicated with intracranial hypertension in a Japanese child. (2014)
  • Author(s): Saida K, Inaba Y, Hirano M, Satake W, Toda T, Suzuki Y, Sudo A, Noda S, Hidaka Y, Hirabayashi K, Imai H, Kurokawa T, Koike K.
  • Journal Title: Brain Dev Volume: 印刷中 Issue: 8 Pages: 721-724
  • DOI: 10.1016/j.braindev.2013.10.013
  • Peer Reviewed / Open Access
• [Journal Article] YY1 binds to α-synuclein 3'-flanking region SNP and stimulates antisense noncoding RNA expression. (2013)
  • Author(s): Mizuta I, Takafuji K, Ando Y, Satake W, Kanagawa M, Kobayashi K, Nagamori S, Shinohara T, Ito C, Yamamoto M, Hattori N, Murata M, Kanai Y, Murayama S, Nakagawa M, Toda T.
  • Journal Title: J Hum Genet Volume: 58 Issue: 11 Pages: 711-719
  • DOI: 10.1038/jhg.2013.90
  • Peer Reviewed
• [Journal Article] Mutations in COQ2 in familial and sporadic multiple-system atrophy. (2013)
  • Author(s): Mitsui J, et. al.
  • Journal Title: N Engl J Med Volume: 369 Issue: 3 Pages: 233-244
  • DOI: 10.1056/nejmoa1212115
  • Peer Reviewed
• [Journal Article] 神経・精神疾患の動向 神経疾患と遺伝子 (2013)
  • Author(s): 佐竹 渉ら
  • Journal Title: 日本医師会雑誌神経・精神疾患診療マニュアル Volume: 142
• [Journal Article] 遺伝性疾患の遺伝子検査 (2013)
  • Author(s): 佐竹 渉
  • Journal Title: Modern Physician Volume: 33 Pages: 625-628
• [Journal Article] ゲノム多様性と神経変性疾患 (2013)
  • Author(s): 佐竹 渉ら
  • Journal Title: 細胞 Volume: 45 Pages: 120-123
• [Journal Article] ゲノムワイド関連解析からの知見とさらなる孤発性パーキンソン病遺伝子の発見へ向けて PARK16、BST1、α-synuclein、LRRK2、Tau (2013)
  • Author(s): 佐竹 渉ら
  • Journal Title: 医学のあゆみ Volume: 247 Pages: 1075-1078
• [Presentation] Genetics-based approach for understanding Parkinson's disease (2016)
  • Author(s): Satake W, Toda T.
  • Organizer: 第57回日本神経学会学術大会
  • Place of Presentation: 神戸
  • Year and Date: 2016-05-18
  • Invited
• [Presentation] Exome Association study and 2nd SNP-GWAS of Parkinson’s disease in Japan (2016)
  • Author(s): Satake W, Suzuki Y, Shigemizu D, .., Kubo M, Sugano S, Matsumoto N, Toda T.
  • Organizer: The 13th International Congress of human Genetics
  • Place of Presentation: Kyoto
  • Year and Date: 2016-04-03
  • Int'l Joint Research
• [Presentation] パーキンソン病のゲノム解析研究 (2016)
  • Author(s): 佐竹渉
  • Organizer: ニューロサイエンスネットワーク
  • Place of Presentation: 神戸
  • Year and Date: 2016-03-18
• [Presentation] Genomic study and subsequent in silico drug discovery for Parkinson’s disease (2016)
  • Author(s): Satake W, Uenaka T, Cha PC, Okada Y, Kashihara K, Murayama S, Hasegawa K, Mochizuki H, Takeda A, Yamamoto M, Murata M, Hattori N, Toda T
  • Organizer: 5th Asian and Oceanian Parkinson’s Disease and Movement Disorders Congress
  • Place of Presentation: Manila
  • Year and Date: 2016-03-11
  • Int'l Joint Research
• [Presentation] Parkinson’s disease Genomics and its Application (2016)
  • Author(s): Satake W, Toda T.
  • Organizer: 第4回これからのパーキンソン病治療を考える会
  • Place of Presentation: 東京
  • Invited
• [Presentation] パーキンソン病の遺伝背景解明とその応用 (2016)
  • Author(s): Satake W, Toda T.
  • Organizer: 兵庫医科大学インテンシブコースセミナー
  • Place of Presentation: 西宮
  • Invited
• [Presentation] Next step of GWAS and Exome study for Parkinson’s disease (2015)
  • Author(s): Satake W, Takeda A, Mochizuki H, Hasegawa K, Yamamoto M, Murata M, Hattori N, Toda T
  • Organizer: 10th Annual Meeting Genetic Epidemiology of Parkinson's disease
  • Place of Presentation: Tokyo
  • Year and Date: 2015-10-01
  • Int'l Joint Research / Invited
• [Presentation] Genome-wide association study (GWAS) in neurodegenerative disorders (2015)
  • Author(s): Satake W
  • Organizer: International Parkinson and Movement Disorder Society Basic Summer School
  • Place of Presentation: Tokyo
  • Year and Date: 2015-08-06
  • Int'l Joint Research / Invited
• [Presentation] Exome Association Study and 2nd SNP-GWAS of Japanese Parkinson's disease (2015)
  • Author(s): Satake W, Ando Y, Suzuki M, Tomiyama H, Nagai Y, Kashihara K, Murayama S, Mochizuki H, Nakashima K, Hasegawa K, Takeda A, Wada K, Tsuji S, Yamamoto M, Murata M, Hattori N, and Toda T.
  • Organizer: 19th International Congress of Parkinson's Disease and Movement Disorders
  • Place of Presentation: San Diego
  • Year and Date: 2015-06-14
  • Int'l Joint Research
• [Presentation] Exome Association Study and 2nd SNP-GWAS of Parkinson's disease (2015)
  • Author(s): Satake W， Ando Y， Suzuki M， Tomiyama H， Nagai Y， Murayama S， Mochizuki H， Nakashima K， Obata F， Hasegawa K， Takeda A， Wada K， Tsuji S， Yamamoto M， Murata M， Hattori N， Toda T
  • Organizer: 第56回日本神経学会学術大会
  • Place of Presentation: 新潟
  • Year and Date: 2015-05-20
• [Presentation] Exome Association study and SNP-GWAS of Parkinson’s disease (2015)
  • Author(s): Satake W, Suzuki Y, Shigemizu D, Cha PC, Tsuji S, Tsunoda T, Kubo M, Sugano S, Matsumoto N, Toda T
  • Organizer: The 11th International workshop on Advanced Genomics; 国際ゲノム会議
  • Place of Presentation: Tokyo
  • Year and Date: 2015-05-20
  • Int'l Joint Research / Invited
• [Presentation] 孤発性パーキンソン病のエクソーム関連解析と第2期SNP-GWAS (2014)
  • Author(s): 佐竹渉、重水大智、鈴木穣 、山本健、富山弘幸、高橋篤、村田美穂、服部信孝、田中敏博 、角田達彦 、久保充明、辻省次、松本直通 、菅野純夫、戸田 達史
  • Organizer: 日本人類伝学会第59回大会
  • Place of Presentation: 東京
  • Year and Date: 2014-11-20 – 2014-11-22
• [Presentation] Risk genes and genome research of sporadic Parkinson’s disease (2014)
  • Author(s): Satake W, Toda T
  • Organizer: The 20th International Congress of Personalized Medicine
  • Place of Presentation: Tokyo
  • Year and Date: 2014-11-15
  • Invited
• [Presentation] Exome Association Study and 2nd SNP-GWAS of Japanese Parkinson’s disease (2014)
  • Author(s): Satake W, Shigemizu D, Suzuki Y, Yamamoto K, Tomiyama H, Yamamoto M, Murata M, Hattori N, Tsunoda T, Kubo M, Tsuji S, Nakamura Y, Sugano S, Toda T.
  • Organizer: American Society of Human Genetics Annual meeting
  • Place of Presentation: San Diego
  • Year and Date: 2014-10-18 – 2014-10-22
• [Presentation] Exome Association Study and 2nd SNP-GWAS of Japanese Parkinson’s disease (2014)
  • Author(s): Satake W, Hasegawa K, Murata M, Hattori N, Toda T.
  • Organizer: Genetic Epidemiology of Parkinson's disease Annual meeting
  • Place of Presentation: Vancouver
  • Year and Date: 2014-09-10 – 2014-09-12
• [Presentation] Exome sequencing of Parkinson's disease in order to identify genetic variants with high disease-risk (2014)
  • Author(s): Satake W, Ando Y, Tomiyama H, Kashihara K, Mochizuki H, Murayama S, Takeda A, Hasegawa K, Tsuji S, Yamamoto M, Murata M, Hattori N, Toda T.
  • Organizer: The MDS 18th International Congress of Parkinson's Disease and Movement Disorders
  • Place of Presentation: Stockholm
  • Year and Date: 2014-06-08 – 2014-06-12
• [Presentation] パーキンソン病感受性遺伝子α-synuiclein SNPとnoncoding RNA (2014)
  • Author(s): 水田依久子、佐竹渉、村山繁雄、金川基、小林千浩、高藤和輝、永森収志、山本光利、服部信孝、村田美穂、金井好克、水野敏樹、中川正法、戸田達史
  • Organizer: 第55回日本神経学会学術大会
  • Place of Presentation: 福岡
  • Year and Date: 2014-05-21 – 2014-05-24
• [Presentation] Exome sequencing of Parkinson's disease in order to identify genetic variants with high disease-risk (2014)
  • Author(s): Satake W et al
  • Organizer: New Frontier of Molecular Neuropathology
  • Place of Presentation: Tokyo, Japan
• [Presentation] Search for rare-variant risks of Parkinson’s disease by sequencing of candidate genes and exome sequencing (2013)
  • Author(s): Satake W et al
  • Organizer: The MDS 17th International Congress of Parkinson's Disease and Movement Disorders
  • Place of Presentation: Sydney, Australia
• [Presentation] Exome sequencing of Parkinson's disease in order to identify genetic variants with high disease-risk (2013)
  • Author(s): Satake W et al
  • Organizer: American Society of Human Genetics Annual meeting
  • Place of Presentation: Boston, USA
• [Presentation] エクソーム解読・一塩基多型解析によるパーキンソン病の遺伝背景の解明 (2013)
  • Author(s): 佐竹渉ら
  • Organizer: 2013年度包括脳ネットワーク夏のワークショップ
  • Place of Presentation: 名古屋
• [Presentation] 剖検脳を用いた孤発性パーキンソン病感受性遺伝子の解析 (2013)
  • Author(s): 上田健博ら
  • Organizer: 第54回日本神経学会学術大会
  • Place of Presentation: 東京
• [Remarks] 神戸大学神経内科
  • URL: http://www.med.kobe-u.ac.jp/im3/rinsyo/shinkei/index.html
• [Remarks] 神戸大学分子脳科学
  • URL: http://www.med.kobe-u.ac.jp/clgene/
• [Remarks] 神戸大学遺伝子診療部
  • URL: http://www.hosp.kobe-u.ac.jp/consultation/guide/department/idenshi.html