Large scale GWAS and exome analyses of intracranial aneurysms

• Project/Area Number: 22241049
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Medical genome science
• Research Institution: National Institute of Genetics
• Principal Investigator: INOUE Ituro 国立遺伝学研究所, 総合遺伝研究系, 教授 (00192500)
• Co-Investigator(Kenkyū-buntansha): YOSHIDA Kenichi 明治大学, 農学部・生命科学科, 准教授 (20345036) ; TAJIMA Atsushi 徳島大学, 大学院・ヘルスバイオサイエンス研究部・人類遺伝学分野, 准教授 (10396864)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥39,910,000 (Direct Cost: ¥30,700,000、Indirect Cost: ¥9,210,000); Fiscal Year 2012: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000); Fiscal Year 2011: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000); Fiscal Year 2010: ¥22,230,000 (Direct Cost: ¥17,100,000、Indirect Cost: ¥5,130,000)
• Keywords: 脳動脈瘤 / ゲノム全域 / アソシエーション・スタディ

Research Abstract

Genome-wide association study for intracranial aneurysm was performed and identified four loci with strong statistical values. Among them, we next focused on 9p21 region, which is also associated with many phenotypes including cardiac infarction. About 250 Mb region was sequenced by next generation sequencers and several SNPs were identified with strong statistical significance. We also performed exome analyses to identify rare variants that explain the pathogenesis of IA in some patients.

Research Products

• [Journal Article] Detection of ancestry informative HLA alleles confirms the admixed origins of Japanese populations. (2013)
  • Author(s): Nakaoka H, Mitsunaga S, Hosomichi K, Shyh-Yuh L, Sawamoto T, Fujiwara T, Tsutsui N, Suematsu K, Shinagawa A, Inoko H, Inoue I.
  • Journal Title: PLoS One Volume: 8
  • DOI: 10.1371/journal.pone.0060793
  • Peer Reviewed
• [Journal Article] Improved loop-mediated isothermal amplification for HLA-DRB1 genotyping using RecA and a restriction enzyme for enhanced amplification. (2013)
  • Author(s): Mitsunaga S, Shimizu S, Okudaira Y, Oka A, Tanaka M, Kimura M, Kulski JK, Inoue I, Inoko H
  • Journal Title: Immunogenetics. Volume: 65(6) Pages: 405-15
  • DOI: 10.1007/s00251-013-0690-0
  • Peer Reviewed
• [Journal Article] ゲノム多様性の形成と維持 (2013)
  • Author(s): 井ノ上 逸朗
  • Journal Title: 細胞 Volume: 45 Pages: 112-115
• [Journal Article] Next-generation sequencing: impact of exome sequencing in characterizing Mendelian disorders (2012)
  • Author(s): Rabbani B, Mahdieh N, Hosomichi K, Nakaoka H, Inoue I
  • Journal Title: J Hum Genet Volume: 57 Pages: 621-632
  • NAID: 10031122239
  • Peer Reviewed
• [Journal Article] Meta-analysis of microarray gene expression studies on intracranial aneurysms (2012)
  • Author(s): Roder C, Kasuya H, Tatagiba M, Inoue I, Krischek B
  • Journal Title: Neuroscience Volume: 201 Pages: 105-113
  • Peer Reviewed
• [Journal Article] Meta-analysis of microarray gene expression studies on intracranial aneurysms. (2012)
  • Author(s): Roder C, et al.
  • Journal Title: Neuroscience Volume: 201 Pages: 105-113
  • DOI: 10.1016/j.neuroscience.2011.10.033
  • Peer Reviewed
• [Journal Article] Next-generation sequencing: impact of exome sequencing in characterizing Mendelian disorders. (2012)
  • Author(s): Rabbani B, et al.
  • Journal Title: J Hum Genet Volume: 57 Pages: 621-632
  • DOI: 10.1038/jhg.2012.91
  • Peer Reviewed
• [Journal Article] 脳外科疾患の遺伝子解析 (2012)
  • Author(s): 井ノ上 逸朗
  • Journal Title: Current Insights in Neurological Science Volume: 19, 20 Pages: 25-27
• [Journal Article] 次世代シーケンサーの臨床応用 (2012)
  • Author(s): 井ノ上 逸朗
  • Journal Title: Medical Technology Volume: 40 Pages: 1551-1551
• [Journal Article] Common variant near the endothelin receptor type A (EDNRA) gene is associated with intracranial aneurysm risk (2011)
  • Author(s): Yasuno K, Bakircioglu M, Low SK, Bilguvar K, Gaal E, Ruigrok YM, Niemela M, Hata A, Bijlenga P, Kasuya H, Jaaskelainen JE, Krex D, Auburger G, Simon M, Krischek B, Ozturk AK, Mane S, Rinkel GJ, Steinmetz H, Hernessnieml J, Schaller K, Zenbutu H, Inoue I, Palotie A, Cambien F, Nakamura Y, Lifton RP, Gunel M.
  • Journal Title: Proc Natl Acad Sci Volume: 108 Pages: 19707-19712
  • DOI: 10.1073/pnas.1117137108
  • Peer Reviewed
• [Journal Article] A systems genetics approach provides a bridge from discovered genetic variants to biological pathways in rheumatoid arthritis. (2011)
  • Author(s): Nakaoka Hirofumi; Cui Tailin; Tajima Atsushi, et al
  • Journal Title: PLoS ONE Volume: 6:9
  • DOI: 10.1371/journal.pone.0025389
  • Peer Reviewed
• [Journal Article] Particular human leukocyte antigen alleles are associated with biochemical traits in the Japanese population (2011)
  • Author(s): Mitsunaga Shigeki; Homma Yasuhiko; Narita Akira, et al
  • Journal Title: Human Immunology Volume: 72:7 Pages: 566-570
  • DOI: 10.1016/j.humimm.2011.03.011
  • Peer Reviewed
• [Journal Article] Exome resequencing combined with linkage analysis identifies novel PTH1R variants in a primary failure of tooth eruption in Japanese (2011)
  • Author(s): Yamaguchi T, Hosomichi K, Narita A, Shirota T, Tomoyasu Y, Maki K, Inoue I.
  • Journal Title: J Bone Miner Res Volume: 26 Pages: 1655-1661
  • Peer Reviewed
• [Journal Article] Germline copy number variations in BRCA1-associated ovarian cancer patients (2011)
  • Author(s): K.Yoshihara, K Tanaka, 他7名
  • Journal Title: Genes Chromosomes Cancer Volume: 50 Pages: 167-177
  • DOI: 10.1002/gcc.20841
  • Peer Reviewed
• [Journal Article] Exome resequencing combined with linkage analysis identifies novel PTH1R variants in a primary failure of tooth eruption in Japanese (2011)
  • Author(s): Yamaguchi T, et al.
  • Journal Title: J Bone Miner Res Volume: (in press)
  • Peer Reviewed
• [Journal Article] IFN-γ and TNF-α Synergistically Induce microRNA-155 Which Regulates TAB2/IP-10 Expression in Human Mesangial Cells (2010)
  • Author(s): Imaizumi T, Tanaka H, Tajima A, Yokono Y, Matsumiya T, Yoshida H, Tsuruga K, Aizawa-Yashiro T, Hayakari R, Inoue I, Ito E, Satoh K
  • Journal Title: Am J Nephrol Volume: 32 Pages: 462-468
  • DOI: 10.1159/000321365
  • Peer Reviewed
• [Journal Article] TRIM39 and RNF39 are associated with Behcet's disease independently of HLA-B*51 and -A*26 (2010)
  • Author(s): Kurata R, Nakaoka H, Tajima A, Hosomichi K, Shiina T, Meguro A, Mizuki N, Ohono S, Inoue I, InokoH
  • Journal Title: Biochem Biophys Res Commun Volume: 401 Pages: 533-537
  • DOI: 10.1016/j.bbrc.2010.09.088
  • Peer Reviewed
• [Journal Article] Genetics of Moyamoya disease (2010)
  • Author(s): Roder C, Nayak NR, Khan N, Tatagiba M, Inoue I, Krischek B.
  • Journal Title: Hum Genet Volume: 55 Pages: 711-716
  • DOI: 10.1038/jhg.2010.103
  • NAID: 10030737392
  • Peer Reviewed
• [Journal Article] Genome wide association analysis of copy number variation in subarachnoid aneurismal hemorrhage (2010)
  • Author(s): Cui T, Inoue I, Shin HD
  • Journal Title: J Hum Genet Volume: 55 Pages: 726-730
  • DOI: 10.1038/jhg.2010.97
  • Peer Reviewed
• [Journal Article] Genome-wide association study to identify genetic variants present in Japanese patients harboring intracranial aneurysms (2010)
  • Author(s): Akiyama K, Narita A, Nakaoka H, Cui T, Takahashi T, Yasuno K, Tajima A, Krischek B, Yamamoto K, Kasuya H, Hata A, Inoue I
  • Journal Title: J Hum Genet Volume: 55 Pages: 656-661
  • DOI: 10.1038/jhg.2010.82
  • NAID: 10030737125
  • Peer Reviewed
• [Journal Article] ANRIL is implicated in the regulation of nucleus and potential transcriptional target of E2F1 (2010)
  • Author(s): Sato K, Nakagawa H, Tajima A, Yoshida K, Inoue I
  • Journal Title: Oncology Rep Volume: 24 Pages: 701-707
  • DOI: 10.3892/or_00000910
  • Peer Reviewed
• [Journal Article] Differential Effects of chromosome 9p21 variation on subphenotypes of intracranial aneurysm: site distribution (2010)
  • Author(s): Nakaoka H, Takahashi T, Akiyama K, Cui T, Tajima A, Krischek B, Kasuya H, Hata A, Inoue I
  • Journal Title: Stroke Volume: 41 Pages: 1593-1598
  • DOI: 10.1161/strokeaha.110.586529
  • Peer Reviewed
• [Journal Article] Association of the Jun dimerization protein 2 gene with intracranial aneurysms in Japanese and Korean cohorts as compared to a Dutch cohort (2010)
  • Author(s): Krischek B, Tajima A, Akagawa H, Narita A, Ruigrok Y, Rinkel G, Wijmenga C, Feigi GC, Kim CJ, Hori T, Tatagiba M, Kasuya H, Inoue I
  • Journal Title: Neuroscience Volume: 169 Pages: 339-343
  • Peer Reviewed
• [Journal Article] Positional effects of polymorphisms in probe-target sequences on genoplot images of oligonucleotide microarrays (2010)
  • Author(s): Cui TL, Nakaoka H, Akiyama K, Kamura H, Hosomichi K, Bae J, Cheong H, Shin H, Yada T, Inoue I
  • Journal Title: Genet Mol Res Volume: 9 Pages: 524-531
  • DOI: 10.4238/vol9-1gmr737
  • Peer Reviewed
• [Journal Article] Genome-wide association study of intracranial aneurysms identifies 5 risk loci (2010)
  • Author(s): Yasuno K, Bilguvar K, Bijlenga P, Kee ALS, Krischek B, Auburger G, Simon M, Krex D, Arlier Z, Nayak N, Ruigrok Y, Niemela M, Tajima A, Frauberg M, Tamas D, Wirjatijasa F, Hata A, Jordi B, Oszvald A, Kasuya H, Gulam Z, Schoch B, Pankaj S, Stuer C, Roelof R, Beck J, Sola T, Ricciardi F, Aromaa A, Illig T, Schreiber S, Duijin CM, Berg LH, Claire P, Carole P, Roder C, Ozturk A, Gaal E, Jeremy W, Berg D, Geisen C, Christoph F, Paul S, Alex F, State MW, Wichmann HE, Breteler MMB, Wijmenga C, Mane S, Juan JE, Sandalcioglu IE, Meyer B, Raabe A, Daniel R, Jaaskelainen A, Hemesniemi J, Rinkel GJE, Zewnbutsu H, Inoue I, Palotie A, Cambien F, Nakamura Y, Lifton RP, Guenel M
  • Journal Title: Nat Genet Volume: 43 Pages: 420-425
  • DOI: 10.1038/ng.563
  • Peer Reviewed
• [Journal Article] Genetics of Moyamoya disease (2010)
  • Author(s): Roder C, et al.
  • Journal Title: J Hum Genet Volume: 55 Pages: 816-821
  • Peer Reviewed
• [Journal Article] Common variants in the ATP2B1 gene are associated with susceptibility to hypertension : The Japanese Millennium Genome Project (2010)
  • Author(s): Tabara Y, et al.
  • Journal Title: Hypertension Volume: 56 Pages: 973-980
  • Peer Reviewed
• [Journal Article] Differential Effects of chromosome 9p21 variation on subphenotypes of intracranial aneurysm : site distribution (2010)
  • Author(s): Nakaoka H, et al.
  • Journal Title: Stroke Volume: 41 Pages: 1593-1598
  • Peer Reviewed
• [Book] 病気はどこで生まれるのか 進化医学でさぐる病気のしくみ(知りたい!サイエンス) (2012)
  • Author(s): 井ノ上逸朗
  • Total Pages: 223
  • Publisher: 技術評論社
• [Book] 病気はどこで生まれるのか 進化医学でさぐる病気のしくみ （知りたい！サイエンス） (2012)
  • Author(s): 井ノ上 逸朗
  • Total Pages: 223
  • Publisher: 技術評論社