Advantage of cohort study with integrated HLA information for personalized medicine

• Project/Area Number: 20K21705
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 58:Society medicine, nursing, and related fields
• Research Institution: Kanazawa University
• Principal Investigator: Hosomichi Kazuyoshi 金沢大学, 医学系, 准教授 (50420948)
• Project Period (FY): 2020-07-30 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2021: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2020: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
• Keywords: HLA遺伝子 / 個別化医療 / コホート研究 / コホート / HLA / ゲノムコホート / 集団遺伝学 / 免疫遺伝学

Outline of Research at the Start

HLA領域はヒトゲノムの中で最も多型性に富み、これまでにゲノムワイド関連解析(GWAS)により多くの疾患や形質と関連することが報告されている。しかし、GWASの研究デザインにおいてHLA領域にはSNPが設定されていないゲノムの空白領域が多く認められ、詳細にHLA領域を解析するには、これに特化したアプローチが必要となる。本研究はヒトの疾患や形質において重要な遺伝要因であるHLA領域について、コホート研究をモデルとし、疾患発症予測など個別化医療における高精度HLAタイピングの有益性を検証する。

Outline of Final Research Achievements

HLA gene diversity is associated with more than 100 diseases including autoimmune diseases. In this study, we used data from health examinations and 37 HLA gene polymorphisms of the Noto area genome cohort residents conducted at Kanazawa University to verify the usefulness of highly accurate HLA typing for disease prediction and other personalized medicine.

Academic Significance and Societal Importance of the Research Achievements

本研究が対象としたゲノムコホート研究は住民の生体サンプルを健診データと共に収集し、既往歴、生化学検査、免疫血清検査、尿検査、血液検査、食事内容など、157項目の形質情報について今後も継続して追跡調査が実施される。このコホート研究においてHLA遺伝子情報を収集したことで、今後の疾患発症のリスクを評価することができ、個人のゲノム情報を医療に活用するモデル集団としての価値を高めることができた。特に花粉症の形質については花粉の種類などによるHLA遺伝子型によるリスクの違いも認められ、詳細な形質情報の収集がHLA遺伝子情報に基づく個別化医療の実現には必要な情報であることが明らかとなった。

Research Products

• [Int'l Joint Research] Universidad San Francisco de Quito(エクアドル)
• [Journal Article] Decoding the diversity of killer immunoglobulin-like receptors by deep sequencing and a high-resolution imputation method (2022)
  • Author(s): Sakaue S, Hosomichi K, Hirata J, Nakaoka H, Yamazaki K, Yawata M, Yawata N, Naito T, Umeno J, Kawaguchi T, Matsui T, Motoya S, Suzuki Y, Inoko H, Tajima A, Morisaki T, Matsuda K, Kamatani Y, Yamamoto K, Inoue I, Okada Y
  • Journal Title: Cell Genomics Volume: 2 Issue: 3 Pages: 100101-100101
  • DOI: 10.1016/j.xgen.2022.100101
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Familial idiopathic basal ganglia calcification with a heterozygous missense variant (c.902C>T/p.P307L) in SLC20A2 showing widespread cerebrovascular lesions (2022)
  • Author(s): Sakai K, Ishida C, Hayashi K, Tsuji N, Kannon T, Hosomichi K, Takei N, Kakita A, Tajima A, Yamada M
  • Journal Title: Neuropathology Volume: 42 Issue: 2 Pages: 126-133
  • DOI: 10.1111/neup.12781
  • Peer Reviewed / Open Access
• [Journal Article] Allelic and haplotypic HLA diversity in indigenous Malaysian populations explored using Next Generation Sequencing (2022)
  • Author(s): Jinam Timothy A.、Hosomichi Kazuyoshi、Nakaoka Hirofumi、Phipps Maude E.、Saitou Naruya、Inoue Ituro
  • Journal Title: Human Immunology Volume: 83 Issue: 1 Pages: 17-26
  • DOI: 10.1016/j.humimm.2021.09.005
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Predictors associated with a better response to the Japanese aluminum-free hepatitis A vaccine, Aimmugen, for people living with HIV. (2021)
  • Author(s): Koga Michiko、Senkoji Tomoe、Kubota Megumi、Ishizaka Aya、Mizutani Taketoshi、Sedohara Ayako、Ikeuchi Kazuhiko、Kikuchi Tadashi、Adachi Eisuke、Saito Makoto、Koibuchi Tomohiko、Hosomichi Kazuyoshi、Ohashi Jun、Kawana‐Tachikawa Ai、Matano Tetsuro、Tsutsumi Takeya、Yotsuyanagi Hiroshi
  • Journal Title: Hepatology Research Volume: 52 Issue: 3 Pages: 227-234
  • DOI: 10.1111/hepr.13736
  • Peer Reviewed / Open Access
• [Journal Article] Whole-Genome Sequencing of a 900-Year-Old Human Skeleton Supports Two Past Migration Events from the Russian Far East to Northern Japan (2021)
  • Author(s): Sato Takehiro、Adachi Noboru、Kimura Ryosuke、Hosomichi Kazuyoshi、Yoneda Minoru、Oota Hiroki、Tajima Atsushi、Toyoda Atsushi、Kanzawa-Kiriyama Hideaki、Matsumae Hiromi、Koganebuchi Kae、Shimizu Kentaro K、Shinoda Ken-ichi、Hanihara Tsunehiko、Weber Andrzej、Kato Hirofumi、Ishida Hajime
  • Journal Title: Genome Biology and Evolution Volume: 13 Issue: 9 Pages: 192-192
  • DOI: 10.1093/gbe/evab192
  • NAID: 120007170565
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] HLA class I allele-lacking leukocytes predict rare clonal evolution to MDS/AML in patients with acquired aplastic anemia. (2021)
  • Author(s): Hosokawa K, Mizumaki H, Yoroidaka T, Maruyama H, Imi T, Tsuji N, Urushihara R, Tanabe M, Zaimoku Y, Nguyen MAT, Tran DC, Ishiyama K, Yamazaki H, Katagiri T, Takamatsu H, Hosomichi K, Tajima A, Azuma F, Ogawa S, Nakao S.
  • Journal Title: Blood Volume: － Issue: 25 Pages: 3576-3580
  • DOI: 10.1182/blood.2020010586
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Polygenic risk scores for low-density lipoprotein cholesterol and familial hypercholesterolemia. (2021)
  • Author(s): Nomura A, Sato T, Tada H, Kannon T, Hosomichi K, Tsujiguchi H, Nakamura H, Takamura M, Tajima A, Kawashiri MA.
  • Journal Title: J Hum Genet. Volume: 66 Issue: 11 Pages: 1079-1087
  • DOI: 10.1038/s10038-021-00929-7
  • Peer Reviewed / Open Access
• [Journal Article] Analysis of HLA gene polymorphisms in East Africans reveals evidence of gene flow in two Semitic populations from Sudan (2021)
  • Author(s): Aamer W, Hassan HY, Nakaoka H, Hosomichi K, Jaeger M, Tahir H, Abdelraheem MH, Netea MG, Inoue I.
  • Journal Title: European Journal of Human Genetics Volume: 印刷中 Issue: 8 Pages: 1259-1271
  • DOI: 10.1038/s41431-021-00845-6
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A novel RFX6 heterozygous mutation (p.R652X) in maturity‐onset diabetes mellitus: A case report (2021)
  • Author(s): Imaki Sakiho、Iizuka Katsumi、Horikawa Yukio、Yasuda Megumi、Kubota Sodai、Kato Takehiro、Liu Yanyan、Takao Ken、Mizuno Masami、Hirota Takuo、Suwa Tetsuya、Hosomichi Kazuyoshi、Tajima Atsushi、Fujiwara Yuuka、Yamazaki Yuji、Kuwata Hitoshi、Seino Yutaka、Yabe Daisuke
  • Journal Title: Journal of Diabetes Investigation Volume: in press Issue: 10 Pages: 1914-1918
  • DOI: 10.1111/jdi.13545
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Characterization of LILRB3 and LILRA6 allelic variants in the Japanese population (2021)
  • Author(s): Hirayasu K, Sun J, Hasegawa G, Hashikawa Y, Hosomichi K, Tajima A, Tokunaga K, Ohashi J, Hanayama R.
  • Journal Title: Journal of Human Genetics Volume: 印刷中 Issue: 7 Pages: 739-748
  • DOI: 10.1038/s10038-021-00906-0
  • Peer Reviewed
• [Journal Article] MCPIP1 reduces HBV-RNA by targeting its epsilon structure (2020)
  • Author(s): Li Yingfang、Que Lusheng、Fukano Kento、Koura Miki、Kitamura Kouichi、Zheng Xin、Kato Takanobu、Aly Hussein Hassan、Watashi Koichi、Tsukuda Senko、Aizaki Hideki、Watanabe Noriyuki、Sato Yuko、Suzuki Tadaki、Suzuki Hiroshi I.、Hosomichi Kazuyoshi、Kurachi Makoto、Wakae Kousho、Muramatsu Masamichi
  • Journal Title: Scientific Reports Volume: 10 Issue: 1 Pages: 20763-20763
  • DOI: 10.1038/s41598-020-77166-z
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A toddler with phylloid-type pigmentary mosaicism and ambiguous genitalia resulting from trisomy 14 induced by a der(Y)t(Y;14) (2020)
  • Author(s): Romero VI, Pozo JC, Saenz S, Llamos-Paneque A, Liehr T, Hosomichi K, Tajima A.
  • Journal Title: Human Genome Variation Volume: 7 Issue: 1 Pages: 28-28
  • DOI: 10.1038/s41439-020-00113-x
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] HLA-B*39:01:01 is a novel risk factor for antithyroid drug-induced agranulocytosis in Japanese population (2020)
  • Author(s): Nakakura S, Hosomichi K, Uchino S, Murakami A, Oka A, Inoue I, Nakaoka H
  • Journal Title: Pharmacogenomics J . Volume: 21 Issue: 1 Pages: 94-101
  • DOI: 10.1038/s41397-020-00187-4
  • Peer Reviewed / Open Access
• [Journal Article] Alopecia areata susceptibility variant in MHC region impacts expressions of genes contributing to hair keratinization and is involved in hair loss (2020)
  • Author(s): Oka A、Takagi A、Komiyama E、Yoshihara N、Mano S、Hosomichi K、Suzuki S、Haida Y、Motosugi N、Hatanaka T、Kimura M、Ueda M、Nakagawa S、Miura H、Ohtsuka M、Tanaka M、Komiyama T、Otomo A、Hadano S、Mabuchi T、Beck S、Inoko H、Ikeda S.
  • Journal Title: EBioMedicine Volume: 57 Pages: 102810-102810
  • DOI: 10.1016/j.ebiom.2020.102810
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A case of MODY5-like manifestations without mutations or deletions in coding and minimal promoter regions of the <i>HNF1B</i> gene (2020)
  • Author(s): Kuwabara-Ohmura Yayoi、Iizuka Katsumi、Liu Yanyan、Takao Ken、Nonomura Kenta、Kato Takehiro、Mizuno Masami、Hosomichi Kazuyoshi、Tajima Atsushi、Miyazaki Tatsuhiko、Horikawa Yukio、Yabe Daisuke
  • Journal Title: Endocrine Journal Volume: 67 Issue: 9 Pages: 981-988
  • DOI: 10.1507/endocrj.EJ20-0038
  • NAID: 130007910088
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed / Open Access
• [Journal Article] A frequent nonsense mutation in exon 1 across certain HLA-A and -B alleles in leukocytes of patients with acquired aplastic anemia. (2020)
  • Author(s): Mizumaki H, Hosomichi K, Hosokawa K, Yoroidaka T, Imi T, Zaimoku Y, Katagiri T, Nguyen MAT, Tran DC, Elbadry MIY, Chonabayashi K, Yoshida Y, Takamatsu H, Ozawa T, Azuma F, Kishi H, Fujii Y, Ogawa S, Tajima A, Nakao S.
  • Journal Title: Haematologica Volume: － Issue: 6 Pages: 247809-247809
  • DOI: 10.3324/haematol.2020.247809
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A Catalog of the Pathogenic Mutations of LDL Receptor Gene in Japanese Familial Hypercholesterolemia (2020)
  • Author(s): Tada H*, Hori M*(*equal contribution), Nomura A, Hosomichi K, Nohara A, Kawashiri M*, Harada-Shiba M*
  • Journal Title: Journal of Clinical Lipidology Volume: - Issue: 3 Pages: 346-351
  • DOI: 10.1016/j.jacl.2020.03.002
  • Peer Reviewed
• [Journal Article] HLA loci predisposing to immune TTP in Japanese: potential role of the shared ADAMTS13 peptide bound to different HLA-DR (2020)
  • Author(s): Sakai K, Kuwana M, Tanaka H, Hosomichi K, Hasegawa A, Uyama H, Nishio K, Omae T, Hishizawa M, Matsui M, Iwato K, Okamoto A, Okuhiro K, Yamashita Y, Itoh M, Kumekawa H, Takezako N, Kawano N, Matsukawa T, Sano H, Ohshiro K, Hayashi K, Ueda Y, Mushino T, Ogawa Y, Yamada Y, Murata M, Matsumoto M.
  • Journal Title: Blood Volume: 135 Issue: 26 Pages: 2413-2419
  • DOI: 10.1182/blood.2020005395
  • Peer Reviewed
• [Journal Article] Subtype-specific gout susceptibility loci and enrichment of selection pressure on ABCG2 and ALDH2 identified by subtype genome-wide meta-analyses of clinically defined gout patients. (2020)
  • Author(s): Nakayama A, Takada T, et al.
  • Journal Title: Ann Rheum Dis. Volume: 79 Issue: 5 Pages: 657665-657665
  • DOI: 10.1136/annrheumdis-2019-216644
  • NAID: 120007042436
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] アマゾン先住民ワオラニ族のHLA遺伝子の多様性 (2021)
  • Author(s): 細道 一善、岩内 陽子、田嶋 敦、 Vanessa Romero
  • Organizer: 第29回 日本組織適合性学会大会
• [Presentation] Genomic Medicine in Japan (2021)
  • Author(s): Kazuyoshi Hosomichi
  • Organizer: The 8th Prince of Songkla University - Kanazawa University Joint Workshop on “ Precision Medicine and Translational Medical Research ”
  • Int'l Joint Research / Invited
• [Presentation] ゲノム解析技術の革新と医学・医療へのインパクト (2020)
  • Author(s): 細道 一善
  • Organizer: 第56回日本移植学会 教育講演
  • Invited
• [Presentation] MHCおよびKIR遺伝子群のNGS解析 (2020)
  • Author(s): 細道 一善
  • Organizer: 日本人類遺伝学会第65回大会 シンポジウム
  • Invited
• [Presentation] Clonal Hematopoiesis By HLA Class I Allele-Lacking Hematopoietic Stem Cells and Concomitant Aberrant Stem Cells Is Rarely Associated with Clonal Evolution to Secondary Myelodysplastic Syndrome and Acute Myeloid Leukemia in Patients with Acquired Aplastic Anemia (2020)
  • Author(s): Hosokawa K, Mizumaki H, Yoroidaka T, Maruyama H, Imi T, Tsuji N, Urushihara R, Tanabe M, Zaimoku Y, Nguyen MAT, Tran DC, Ishiyama K, Yamazaki H, Katagiri T, Hosomichi K, Tajima A, Azuma F, Ogawa S, Nakao S
  • Organizer: 62nd ASH Annual Meeting
  • Int'l Joint Research
• [Book] ヒトゲノム事典 (2021)
  • Author(s): 井ノ上 逸朗, 今西 規, 河村 正二, 斎藤 成也, 颯田 葉子, 田嶋 敦
  • Total Pages: 448
  • Publisher: 一色出版
  • ISBN: 4910389121
• [Book] 月刊糖尿病【全容が解き明かされつつある糖尿病遺伝素因】次世代シークエンサー(NGS)による新規糖尿 病遺伝子同定のピットフォール ~in silico解析による意義不明変異(VUS)の取り扱いについて~ (2020)
  • Author(s): 細道一善
  • Total Pages: 7
  • Publisher: 医学出版