Identification of biomarkers of autoimmune diseases using HLA imputation

• Project/Area Number: 15H05670
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Collagenous pathology/Allergology
• Research Institution: Osaka University (2016-2017); Tokyo Medical and Dental University (2015)
• Principal Investigator: Okada Yukinori 大阪大学, 医学系研究科, 教授 (70727411)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥23,920,000 (Direct Cost: ¥18,400,000、Indirect Cost: ¥5,520,000); Fiscal Year 2017: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000); Fiscal Year 2016: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000); Fiscal Year 2015: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000)
• Keywords: 遺伝統計学 / HLA遺伝子 / バイオインフォマティクス / ゲノム / MHC領域 / HLA imputation法 / 疾患ゲノム解析 / 自己免疫疾患

Outline of Final Research Achievements

The major histocompatibility complex (MHC) region at chromosome 6 defines risk of a variety of human complex diseases. The HLA imputation method can computationally impute HLA gene variants from the single nucleotide polymorphism (SNP) genotype data in the MHC region. By constructing the HLA imputation reference panel of the Japanese population (n = 900), we conducted HLA imputation analysis for the genome-wide association study (GWAS) data of autoimmune diseases including rheumatoid arthritis and Graves’ disease, which provided biomarker HLA variants with disease risk.

Research Products

• [Int'l Joint Research] Harvard Medical School/Broad Institute(米国)
• [Int'l Joint Research] Sanger Institute(英国)
• [Int'l Joint Research] Broad Institute/Harvard Medical School(米国)
• [Int'l Joint Research] Sanger Institute/Cambridge University(英国)
• [Journal Article] Genetic analysis of quantitative traits in the Japanese population links cell types to complex human diseases (2018)
  • Author(s): Kanai M, Akiyama M, Takahashi A, Matoba N, Momozawa Y, Ikeda M, Iwata N, Ikegawa S, Hirata M, Matsuda K, Kubo M, Okada Y, Kamatani Y
  • Journal Title: Nat Genet Volume: 50 Issue: 3 Pages: 390-400
  • DOI: 10.1038/s41588-018-0047-6
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Statist ical genetics and its application to neuroimmunology (2018)
  • Author(s): Ogawa K, Okada Y
  • Journal Title: Clin Exp Neurol Volume: 9 Issue: 1 Pages: 7-12
  • DOI: 10.1111/cen3.12445
  • Peer Reviewed / Open Access
• [Journal Article] Variants at HLA-A, HLA-C, and HLA-DQB1 confer risk of psoriasis vulgaris in Japanese. (2018)
  • Author(s): Hirata J, --- Saeki H, et al
  • Journal Title: J Invest Dermatol Volume: 138 Issue: 3 Pages: 542-548
  • DOI: 10.1016/j.jid.2017.10.001
  • NAID: 120007134453
  • Peer Reviewed / Open Access
• [Journal Article] Genome-wide association study identifies 112 new loci for body mass index in the Japanese population (2017)
  • Author(s): Akiyama M, Okada Y, Kanai M, Takahashi A, Momozawa Y, Ikeda M, Iwata N, Ikegawa S, Hirata M, Matsuda K, Iwasaki M, Yamaji T, Sawada N, Hachiya T, Tanno K, Shimizu A, Hozawa A, Minegishi N, Tsugane S, Yamamoto M, Kubo M and Kamatani Y
  • Journal Title: Nat Genet Volume: 49 Issue: 10 Pages: 1458-1462
  • DOI: 10.1038/ng.3951
  • Peer Reviewed / Open Access
• [Journal Article] Polygenic burdens on cell-specific pathways underlie the risk of rheumatoid arthritis (2017)
  • Author(s): Ishigaki Kazuyoshi、Kochi Yuta、Suzuki Akari、Tsuchida Yumi、Tsuchiya Haruka、Sumitomo Shuji、Yamaguchi Kensuke、Nagafuchi Yasuo、Nakachi Shinichiro、Kato Rika、Sakurai Keiichi、Shoda Hirofumi、Ikari Katsunori、Taniguchi Atsuo、Yamanaka Hisashi、Miya Fuyuki、Tsunoda Tatsuhiko、et al.、Yamamoto Kazuhiko
  • Journal Title: Nature Genetics Volume: 49 Issue: 7 Pages: 1120-1125
  • DOI: 10.1038/ng.3885
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The Rheumatoid Arthritis Risk Variant CCR6DNP Regulates CCR6 via PARP-1. (2016)
  • Author(s): Li G, Cunin P, Wu D, Diogo D, Yang Y, Okada Y, Plenge RM, Nigrovic PA
  • Journal Title: PLoS Genet Volume: 12 Issue: 9 Pages: e1006292-e1006292
  • DOI: 10.1371/journal.pgen.1006292
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Trans-ethnic Fine Mapping Highlights Kidney-Function Genes Linked to Salt Sensitivity. (2016)
  • Author(s): Mahajan A, Rodan AR, Le TH, Gaulton KJ, Haessler J, ..., Okada Y, Laurie CC, Morris AP, Franceschini N
  • Journal Title: Am J Hum Gen Volume: 99 Issue: 3 Pages: 636-646
  • DOI: 10.1016/j.ajhg.2016.07.012
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Association of variations in HLA class II and other loci with susceptibility to EGFR-mutated lung adenocarcinoma. (2016)
  • Author(s): Shiraishi K, Okada Y 他44名 Inazawa J 38番目
  • Journal Title: Nat Commun. Volume: 7 Issue: 1 Pages: 12451-12451
  • DOI: 10.1038/ncomms12451
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Contribution of a Non-classical HLA Gene, HLA-DOA, to the Risk of Rheumatoid Arthritis (2016)
  • Author(s): Okada Y, Suzuki A, Ikari K, Terao C, Kochi Y, Ohmura K, Higasa K, Akiyama M, Ashikawa K, Kanai M, Hirata J, Suita N, Teo YY, Xu H, Bae SC, Takahashi A, Momozawa Y, Matsuda K, Momohara S, Taniguchi A, Yamada R, Mimori T, Kubo M, Brown MA, Raychaudhuri S, Matsuda F, Yamanaka H, Kamatani Y, Yamamoto K
  • Journal Title: Am J Hum Genet Volume: 99 Issue: 2 Pages: 366-374
  • DOI: 10.1016/j.ajhg.2016.06.019
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Genetic risk of extranodal natural killer T-cell lymphoma: a genome-wide association study. (2016)
  • Author(s): Li Z, Xia Y, Feng LN, Chen JR, Li HM, Cui J, Cai QQ, Sim KS, ..., Okada Y, Raychaudhuri S, Lim ST, Tan W, Peng RJ, Khor CC, Bei JX
  • Journal Title: Lancet Oncol Volume: 17 Issue: 9 Pages: 1240-1247
  • DOI: 10.1016/s1470-2045(16)30148-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Empirical estimation of genome-wide significance thresholds based on the 1000 Genomes Project data set (2016)
  • Author(s): Kanai M, Tanaka T, Okada Y
  • Journal Title: J Hum Genet Volume: 61 Issue: 10 Pages: 861-866
  • DOI: 10.1038/jhg.2016.72
  • NAID: 40020966136
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Systematic analysis of mutation distribution in three dimensional protein structures identifies cancer driver genes (2016)
  • Author(s): Fujimoto A, Okada Y, Boroevich KA, Tsunoda T, Taniguchi H, Nakagawa H
  • Journal Title: Sci Rep Volume: 6 Issue: 1 Pages: 26483-26483
  • DOI: 10.1038/srep26483
  • NAID: 120005774574
  • Peer Reviewed / Open Access
• [Journal Article] Significant impact of miRNA-target gene networks on genetics of human complex traits. (2016)
  • Author(s): Okada Y, Muramatsu T, Suita N, Kanai M, Kawakami E et al.
  • Journal Title: Sci Rep Volume: 6 Issue: 1 Pages: 22223-22223
  • DOI: 10.1038/srep22223
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Genome-wide association studies in the Japanese population identify seven novel loci for type 2 diabetes. (2016)
  • Author(s): Imamura M, ・・Yamauchi T,・・ Shojima N, ・・Kadowaki T
  • Journal Title: Nat Commun. Volume: 7 Issue: 1 Pages: 10531-10531
  • DOI: 10.1038/ncomms10531
  • NAID: 120006889946
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] High-density genotyping of immune-related loci identifies new SLE risk variants in individuals with Asian ancestry (2016)
  • Author(s): 76.Imamura M, Takahashi A, Yamauchi T, Hara K, Yasuda K, ... Okada Y et al.
  • Journal Title: Nat Genet Volume: 48 Issue: 3 Pages: 323-330
  • DOI: 10.1038/ng.3496
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Ethnically shared and heterogeneous impacts of molecular pathways suggested by the genome-wide meta-analysis of rheumatoid arthritis. (2016)
  • Author(s): Okada Y, Raj T, Yamamoto K.
  • Journal Title: Rheumatology Volume: 22 Issue: 1 Pages: 186-189
  • DOI: 10.1093/rheumatology/kev314
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Anti-citrullinated peptide/protein antibody (ACPA)-negative RA shares a large proportion of susceptibility loci with ACPA-positive RA: a meta-analysis of genome-wide association study in a Japanese population. (2015)
  • Author(s): Terao C, Ohmura K, Kochi Y, Ikari K, Okada Y, Shimizu M, , Kubo M, Yamada R, Taniguchi A, Yamanaka H, Momohara S, Yamamoto K, Mimori T, Matsuda F.
  • Journal Title: Arthritis Res Ther Volume: 17 Issue: 1 Pages: 104-104
  • DOI: 10.1186/s13075-015-0623-4
  • NAID: 120005749954
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Widespread non-additive and interaction effects within HLA loci modulate the risk of autoimmune diseases. (2015)
  • Author(s): Lenz TL, Deutsch AJ, Han B, Hu X, Okada Y et al.
  • Journal Title: Nat Genet Volume: 47 Issue: 9 Pages: 1085-1090
  • DOI: 10.1038/ng.3379
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Directional dominance on stature and cognition in diverse human populations (2015)
  • Author(s): Joshi PK, Esko T, Mattsson H, Eklund N, Gandin I, ... Okada Y et al.
  • Journal Title: Nature Volume: 523 Issue: 7561 Pages: 459-462
  • DOI: 10.1038/nature14618
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Partitioning heritability by functional annotation using genome-wide association summary statistics (2015)
  • Author(s): Finucane HK, Bulik-Sullivan B, Gusev A, Trynka G, Reshef Y, ... Okada Y et al.
  • Journal Title: Nat Genet Volume: 47 Issue: 11 Pages: 1228-1235
  • DOI: 10.1038/ng.3404
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Identification of the risk HLA variants of Graves' disease by applying the HLA imputation method to large scale Japanese genome-wide association study data (2015)
  • Author(s): Okada Y, Momozawa Y, Ashikawa K, Kanai M, Matsuda K et al.
  • Organizer: 17th Asia Pacific League of Associations for Rheumatology Congress
  • Place of Presentation: Chennai, India
  • Year and Date: 2015-09-05
  • Int'l Joint Research