Exploring rare variants associated with pediatric asthma for personalized medicine by exome analysis

• Project/Area Number: 24390251
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: University of Tsukuba
• Principal Investigator: Noguchi Emiko 筑波大学, 医学医療系, 教授 (40344882)
• Co-Investigator(Kenkyū-buntansha): Okamura Koji 国立成育医療研究センター, システム発生再生医学研究部, 室長 (80456194)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000); Fiscal Year 2014: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2013: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
• Keywords: エクソーム / アレルギー / 気管支喘息

Outline of Final Research Achievements

The aim of this study is to investigate rare variants associated with asthma by exome analysis using next generation sequencer. We performed exome analyses on 67 patients who were diagnosed with asthma. Control genotype/allele frequencies were obtained from Human Genetic Variation Database. In the genomic regions which were identified to be associated with asthma by genome-wide association studies, we found two missense variants (one in IL1RL1 and the other in GSDMB) to be possibly associated with asthma (P < 0.05). We also found several candidate rare variants to be associated with asthma.

Research Products

• [Journal Article] Variants near the HLA complex group 22 gene (HCG22) confer increased susceptibility to late-onset asthma in Japanese populations. (2016)
  • Author(s): Yatagai Y, Hirota T, Sakamoto T, Yamada H, Masuko H, Kaneko Y, Iijima H, Naito T, Noguchi E, Tamari M, Kubo M, Takahashi A, Konno S, Makita H, Nishimura M, Hijikata M, Keicho N, Homma S, Taguchi Y, Azuma A, Kudoh S, Hizawa N.
  • Journal Title: J Allergy Clin Immunol Volume: 印刷中 Issue: 1 Pages: 281-283
  • DOI: 10.1016/j.jaci.2015.11.023
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Role of Lung Function Genes in the Development of Asthma (2015)
  • Author(s): Yamada H, Masuko H, Yatagai Y, Sakamoto T, Kaneko Y, Iijima H, Naito T, Noguchi E, Konno S, Nishimura M, Hirota T, Tamari M, Hizawa N
  • Journal Title: PLoS One Volume: － Issue: 1 Pages: e0145832-e0145832
  • DOI: 10.1371/journal.pone.0145832
  • NAID: 120007129828
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Identification and Characterization of CD300H, a New Member of the Human CD300 Immunoreceptor Family (2015)
  • Author(s): Niizuma K, Tahara-Hanaoka S, Noguchi E, Shibuya A.
  • Journal Title: J. Biol. Chem, 290(36):22298-22308, 2015 Volume: 290 Issue: 36 Pages: 22298-22308
  • DOI: 10.1074/jbc.m115.643361
  • NAID: 120007136146
  • Peer Reviewed / Open Access
• [Journal Article] T-cell-restricted T-bet overexpression induces aberrant hematopoiesis of myeloid cells and impairs function of macrophages in the lung (2015)
  • Author(s): Iriguchi S, Kikuchi N, Kaneko S, Noguchi E, Morishima Y, Matsuyama M, Yoh K, Takahashi S, Nakauchi H, Ishii Y
  • Journal Title: Blood Volume: 125 Issue: 2 Pages: 370-82
  • DOI: 10.1182/blood-2014-05-575225
  • Peer Reviewed / Open Access
• [Journal Article] Influence of MILR1 promoter polymorphism on expression levels and the phenotype of atopy. (2014)
  • Author(s): Nanatsue K, Ninomiya T, Tsuchiya M, Tahara-Hanaoka S, Shibuya A, Masuko H, Sakamoto T, Hizawa N, Arinami T, Noguchi E.
  • Journal Title: J Hum Genet Volume: 59(9) Issue: 9 Pages: 480-483
  • DOI: 10.1038/jhg.2014.57
  • Peer Reviewed
• [Journal Article] Genomewide association study identifies HAS2 as a novel susceptibility gene for adult asthma in a Japanese population (2014)
  • Author(s): Yatagai Y, Sakamoto T, Yamada H, Masuko H, Kaneko Y, Iijima H, Naito T, Noguchi E, Hirota T, Tamari M, Konno S, Nishimura M, Hizawa N
  • Journal Title: Clin Exp Allergy Volume: 44 Issue: 11 Pages: 1327-1334
  • DOI: 10.1111/cea.12415
  • Peer Reviewed
• [Journal Article] Genome-wide association study for levels of total serum IgE identifies HLA-C in a Japanese population (2013)
  • Author(s): Yatagai Y, Sakamoto T, Masuko H, et al
  • Journal Title: PLoS One Volume: 8(12) Issue: 12 Pages: 1-9
  • DOI: 10.1371/journal.pone.0080941
  • Peer Reviewed
• [Journal Article] Genetic polymorphisms in the IL22 gene are associated with psoriasis vulgaris in a Japanese population. (2013)
  • Author(s): Saeki H, Hirota T, Nakagawa H, Tsunemi Y, Kato T, Shibata S, Sato S, Doi S, Miyatake A, Ebe K, Noguchi E, Ebihara T, Amagaii M, Esaki H, Takeuchi S, Furue M, Nakamura Y, Tamari M.
  • Journal Title: J Dermatol Sci. Volume: 71 Issue: 2 Pages: 148-150
  • DOI: 10.1016/j.jdermsci.2013.04.002
  • Peer Reviewed
• [Journal Article] Functional analysis of BRCA1 missense variants of uncertain significance in Japanese breast cancer families (2013)
  • Author(s): Kawaku S1, Sato R, Song H, Bando Y, Arinami T, Noguchi E.
  • Journal Title: J Hum Genet Volume: 58(9) Issue: 9 Pages: 648-621
  • DOI: 10.1038/jhg.2013.71
  • NAID: 10031195299
  • Peer Reviewed
• [Journal Article] Asthma Phenotypes in Japanese Adults - Their Associations with the <i>CCL5</i> and <i>ADRB2</i> Genotypes (2013)
  • Author(s): Kaneko Y
  • Journal Title: Allergology International Volume: 62 Issue: 1 Pages: 113-121
  • DOI: 10.2332/allergolint.12-OA-0467
  • NAID: 130004477174
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed
• [Journal Article] Prevalence of atopic dermatitis in Japanese infants treated with moisturizer since birth and its relation to FLG mutations (2013)
  • Author(s): Inoue Y, Nakagawara R, Kambara T, Tanaka K, Seki K, Enomoto H, Noguchi E, Aihara M, Ikezawa Z
  • Journal Title: Eur J Dermatol Volume: 23(2) Issue: 2 Pages: 288-289
  • DOI: 10.1684/ejd.2013.1960
  • Peer Reviewed
• [Journal Article] Cystatin SN upregulation in patients with seasonal allergic rhinitis (2013)
  • Author(s): Imoto Y, Tokunaga T, Matsumoto Y, et al
  • Journal Title: PLoS One Volume: 8(8) Issue: 8 Pages: e67057-e67057
  • DOI: 10.1371/journal.pone.0067057
  • Peer Reviewed
• [Journal Article] A Distinct Sensitization Pattern Associated with Asthma and the Thymic Stromal Lymphopoietin (<i>TSLP</i>) Genotype (2013)
  • Author(s): Iijima H
  • Journal Title: Allergology International Volume: 62 Issue: 1 Pages: 123-130
  • DOI: 10.2332/allergolint.12-OA-0488
  • NAID: 130004477178
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed
• [Journal Article] A Distinct Sensitization Pattern Associated with Asthma and the Thymic Stromal Lymphopoietin (TSLP) Genotype (2013)
  • Author(s): Iijima H, Kaneko Y; Yamada H, Yatagai Y, Masuko H, Sakamoto T, Naito T, Hirota T, Tamari M, Konno S, Nishimura M, Noeuchi E, Hizawa N
  • Journal Title: Allergol Int Volume: 62 Pages: 123-130
  • Peer Reviewed
• [Journal Article] Genome-wide association study identifies eight new susceptibility loci for atopic dermatitis in the Japanese population. (2012)
  • Author(s): Hirota T
  • Journal Title: Nat Genet Volume: 44 Issue: 11 Pages: 1222-6
  • DOI: 10.1038/ng.2438
  • Peer Reviewed
• [Journal Article] Generation of induced pluripotent stem cells from human nasal epithelial cells using a Sendai virus vector (2012)
  • Author(s): Ono M, Hamada Y, Horiuchi Y, Matsuo-Takasaki M, Imoto Y, Satomi K, Arinami T, Hasegawa M, Fujioka T, Nakamura Y, Noguchi E
  • Journal Title: PLoS One Volume: 7 Issue: 8 Pages: e42855-e42855
  • DOI: 10.1371/journal.pone.0042855
  • Peer Reviewed
• [Journal Article] Association of adiponectin polymorphism with cord blood adiponectin concentrations and intrauterine growth (2012)
  • Author(s): Saito M, Kamoda T, Nishimura K, Miyazono Y, Kanai Y, Kato Y, Iwabuchi A, Fukushima H, Hamada H, Arinami T, Sumazaki R, Noeuchi E
  • Journal Title: J Hum Genet Volume: 57 Pages: 109-114
  • Peer Reviewed
• [Presentation] 次世代シークエンサーを用いたゲノム解析 (2015)
  • Author(s): 野口恵美子
  • Organizer: 第64回日本アレルギー学会学術大会
  • Place of Presentation: 東京 グランドプリンスホテル新高輪
  • Year and Date: 2015-05-27
  • Invited
• [Presentation] 次世代シークエンサーとアレルギー疾患：どのように使えるのか？ (2014)
  • Author(s): 野口恵美子
  • Organizer: 第26回日本アレルギー学会春季臨床大会
  • Place of Presentation: 東京
  • Year and Date: 2014-05-09
  • Invited
• [Presentation] 中高年発症喘息（late onset asthma：LOA）を対象とした網羅的遺伝子解析 (2014)
  • Author(s): 谷田貝洋平 山田英恵 金子美子 増子裕典 坂本 透 野口恵美子 飯島弘晃 内藤隆志 広田朝光 玉利真由美 檜澤伸之
  • Organizer: 第26回日本アレルギー学会春季臨床大会
  • Place of Presentation: 東京
  • Year and Date: 2014-05-09
• [Presentation] 健常人における吸入抗原のアレルギー感作に対するゲノム網羅的関連解析 (2014)
  • Author(s): 山田英恵 谷田貝洋平 増子裕典 飯島弘晃 内藤隆志 坂本 透 野口恵美子 広田朝光 玉利真由美 檜澤伸之
  • Organizer: 第26回日本アレルギー学会春季臨床大会
  • Place of Presentation: 東京
  • Year and Date: 2014-05-09
• [Presentation] アトピー性疾患の感受遺伝子探索：次世代シークエンサーの管理と今後課題 (2013)
  • Author(s): 野口恵美子
  • Organizer: 東京女子医科大学第９回 テニュアトラック教員支援セミナー
  • Place of Presentation: 東京
  • Invited
• [Presentation] アトピー素因ってなんだろう」～アレルギーは遺伝するの？ (2013)
  • Author(s): 野口恵美子
  • Organizer: 第30回日本難治性喘息・アレルギー疾患学会
  • Place of Presentation: 茨城県つくば市
  • Invited
• [Presentation] 次世代シークエンサのアレルギー疾患研究への応用 (2012)
  • Author(s): 野口 恵美子
  • Organizer: 第24回アレルギー学会春季臨床大会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2012-05-12