Identification of Japanese-specific SNP in exfoliation glaucoma patients with genome-wide association analysis of 1000K microarray

• Project/Area Number: 23592582
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: IKEDA YOKO 京都府立医科大学, 医学(系)研究科(研究院), 客員講師 (00433243)
• Co-Investigator(Kenkyū-buntansha): TASHIRO Kei 京都府立医科大学, 医学研究科, 教授 (10263097) ; KINOSHITA Shigeru 京都府立医科大学, 医学研究科, 教授 (30116024) ; MORI Kazuhiko 京都府立医科大学, 医学研究科, 講師 (40252001) ; NAKANO Masakazu 京都府立医科大学, 医学研究科, 准教授 (70381944)
• Co-Investigator(Renkei-kenkyūsha): IMAI Kojiro 京都府立医科大学, 医学研究科 医療フロンティア展開学, 講師 (70728443)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 落屑緑内障 / 全ゲノム解析 / 遺伝子 / 緑内障 / ゲノムワイドアソシエイション

Research Abstract

We performed a genome-wide association study (GWAS) using 898 samples obtained from Japanese subjects [201 exfoliation syndrome (XFS)/exfoliation glaucoma (XFG) patients and 697 control subjects] by means of 1000K Affymetrix (Santa Clara, CA) microarray. As a result, we identified 34 genome-wide significant single-nucleotide polymorphisms (SNPs) distributed in not only LOXL1 but also in two other genes in the locus. These results were confirmed by analyzing an independent Japanese population consisted of 121 exfoliation syndrome/glaucoma patients and 263 controls. We performed a meta analysis by combining the results of the GWAS and its replication analysis, and we finally obtained 34 SNPs that passed the Bonferroni correction. These results suggested that the combination of newly discovered SNPs might be useful for precise XFG risk assessment, as well as for elucidating the molecular mechanism of XFG pathogenesis through XFS.

Research Products

• [Journal Article] Novel common variants and susceptible haplotype for exfoliation glaucoma specific to Asian population (2014)
  • Author(s): Nakano M, Ikeda Y, Tokuda Y, Fuwa M, Ueno M, Imai K, Sato R, Omi N, Adachi H, Kageyama M, Mori K, Kinoshita S,Tashiro K
  • Journal Title: Sci Rep Volume: 4 Issue: 1 Pages: 5340-5340
  • DOI: 10.1038/srep05340
  • Peer Reviewed / Open Access
• [Journal Article] Morphological analysis of age-related iridocorneal angle changes in normal and glaucomatous cases using anterior segment optical coherence tomography (2014)
  • Author(s): Maruyama Y, Mori K, Ikeda Y, Ueno M, Kinoshita S
  • Journal Title: Clinical Ophthalmology Volume: 8 Pages: 1-6
  • Peer Reviewed
• [Journal Article] Effects of Long-Term Topical Prostaglandin Therapy on Central Corneal Thickness (2014)
  • Author(s): Maruyama Y, Mori K, Ikeda Y, Ueno M, Kinoshita S
  • Journal Title: J Ocul Pharmacol Ther Volume: (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Effects of Long-Term Topical Prostaglandin Therapy on Central Corneal Thickness. (2014)
  • Author(s): Maruyama Y, Mori K, Ikeda Y, Ueno M, Kinoshita S.
  • Journal Title: J Ocul Pharmacol Ther. Volume: Epub ahead of print
  • Peer Reviewed
• [Journal Article] Morphological analysis of age-related iridocorneal angle changes in normal and glaucomatous cases using anterior segment optical coherence tomography. (2014)
  • Author(s): Maruyama Y, Mori K, Ikeda Y, Ueno M, Kinoshita S.
  • Journal Title: Clinical Ophthalmology Volume: 8 Pages: 113-118
  • DOI: 10.2147/opth.s52370
  • Peer Reviewed
• [Journal Article] 白内障術後に生じた遅発型水晶体起因性続発緑内障の4例 (2013)
  • Author(s): 多田香織、上野盛夫、森和彦、池田陽子、今井浩二郎、木下茂
  • Journal Title: あたらしい眼科 Volume: 30(4) Pages: 569-572
  • NAID: 10031168125
  • Peer Reviewed
• [Journal Article] 円蓋部基底線維柱帯切除術後における留置糸に関連した微小膿瘍様病変の検討 (2013)
  • Author(s): 加藤弘明、森和彦、池田陽子、生島徹、小林ルミ、今井浩二郎、木下茂
  • Journal Title: あたらしい眼科 Volume: 30(3) Pages: 401-404
  • NAID: 10031162332
  • Peer Reviewed
• [Journal Article] 円蓋部基底線維柱帯切除術後における留置糸に関連した微小膿瘍様病変の検討. (2013)
  • Author(s): 加藤 弘明、森 和彦、池田 陽子、生島 徹、小林 ルミ、今井 浩二郎、木下 茂.
  • Journal Title: あたらしい眼科 Volume: 30(3) Pages: 401-404
  • NAID: 10031162332
  • Peer Reviewed
• [Journal Article] Common variants in CDKN2B-AS1 associated with optic-nerve vulnerability of glaucoma identified by genome-wide association studies in Japanese. (2012)
  • Author(s): Nakano, M., Ikeda, Y., Tokuda, Y., Fuwa, M., Omi, N., Ueno, M., Imai, K., Adachi, H., Kageyama, M., Mori, K., Kinoshita, S. and Tashiro, K.
  • Journal Title: PLoS ONE Volume: 7
  • Peer Reviewed
• [Journal Article] An approach to predict the risk of glaucoma development by integrating different attribute data. (2012)
  • Author(s): Tokuda, Y., Yagi, T., Yoshii, K., Ikeda, Y., Fuwa, M., Ueno, M., Nakano, M., Omi, N., Tanaka, M., Mori, K., Kageyama, M. Nagasaki, I., Yagi, K., Kinoshita, S. and Tashiro, K
  • Journal Title: SpringerPlus Volume: 1 Pages: 41-41
  • Peer Reviewed
• [Journal Article] Expression of prostaglandin F receptor in scleral and subconjunctival tissue. (2012)
  • Author(s): Imai, K., Ueta, M., Mori ,K., Ueno, M., Ikeda, Y., Oga, T., Yokoi, N., Shinomiya, K., Narumiya, S., Kinoshita, S.
  • Journal Title: Br. J. Ophthalmol Volume: 96 Pages: 1148-1149
  • Peer Reviewed
• [Journal Article] 3種類の緑内障視野進行プログラムの比較検討 (2012)
  • Author(s): 吉川晴菜, 森 和彦, 池田陽子,上野盛夫, 木下 茂
  • Journal Title: あたらしい眼科 Volume: 29 Pages: 840-843
  • Peer Reviewed
• [Journal Article] 緑内障セミナー．「緑内障Genome-Wide Association Study 最新の知見：１．どう見て、どう考えるか」 (2012)
  • Author(s): 池田陽子, 中野正和, 森 和彦
  • Journal Title: あたらしい眼科 Volume: 29 Pages: 209-210
• [Journal Article] Common Variants in CDKN2B-AS1 Associated with Optic-Nerve Vulnerability of Glaucoma Identified by Genome-Wide Association Studies in Japanese. (2012)
  • Author(s): Masakazu Nakano*, Yoko Ikeda*, Yuichi Tokuda* et al. ( * equal contoribution)
  • Journal Title: PloS 1 Volume: 7
  • Peer Reviewed
• [Journal Article] 緑内障セミナー．「緑内障Genome-Wide Association Study最新の知見：1.どう見て、どう考えるか」 (2012)
  • Author(s): 池田陽子、中野正和、森 和彦
  • Journal Title: あたらしい眼科 Volume: 29 Pages: 209-210
• [Journal Article] 緑内障セミナー．「緑内障Genome-Wide Association Study最新の知見：2.次世代シーケンサーをいかに活用するか」 (2012)
  • Author(s): 中野正和、池田陽子、森 和彦
  • Journal Title: あたらしい眼科 Volume: 29 Pages: 355-357
• [Journal Article] 【眼科診療:5年前の常識は,現在の非常識!】 緑内障 スペシャルレクチャー 緑内障の遺伝子(解説/特集). (2011)
  • Author(s): 池田陽子、中野正和、森 和彦
  • Journal Title: 臨床眼科 Volume: 65 Pages: 238-241
• [Presentation] 線維柱帯切除術後のプロスタグランジン製剤点眼中止に伴う中心角膜厚変化の検討 (2014)
  • Author(s): 池田陽子、森和彦、上野盛夫、吉川晴菜、丸山悠子、木下茂
  • Organizer: 第37回日本眼科手術学会総会
  • Place of Presentation: 京都
• [Presentation] 線維柱帯切除術後のプロスタグランジン製剤点眼中止に伴う中心角膜厚変化の検討. (2014)
  • Author(s): 池田陽子、森 和彦 、上野盛夫 、吉川晴菜 、丸山悠子 、木下 茂.
  • Organizer: 第37回 日本眼科手術学会総会
  • Place of Presentation: 京都
• [Presentation] 正常者前房隅角因子の加齢による減少スピードの検討 (2013)
  • Author(s): 池田陽子,森和彦,上野盛夫,吉川晴菜,加藤浩晃,丸山悠子,木下茂
  • Organizer: 第67回日本臨床眼科学会
  • Place of Presentation: 横浜
  • Year and Date: 2013-11-01
• [Presentation] 落屑緑内障患者における血液生化学的データの解析 (2013)
  • Author(s): 池田陽子,森和彦,上野盛夫,吉川晴菜,加藤浩晃,丸山悠子,吉井健悟,中野正和,田代啓,木下茂
  • Organizer: 第24回日本緑内障学会
  • Place of Presentation: 東京
  • Year and Date: 2013-09-22
• [Presentation] Analysis of Ophthalmic Clinical Data Association for CDKN2B-AS1 Genotype in Normal Subjects (2013)
  • Author(s): Ikeda Y, Mori K, Ueno M, Nakano M, Tokuda Y, Omi N, Sato R, Yoshii K, Tashiro K, Kinoshita S
  • Organizer: ARVO
  • Place of Presentation: Seattle
  • Year and Date: 2013-05-06
• [Presentation] 正常者におけるCDKN2B-AS1のジェノタイプ別臨床データの解析 (2013)
  • Author(s): 池田陽子,森和彦,上野盛夫,中野正和,吉井健悟,徳田雄市,大見奈津江,佐藤隆一,田代啓,木下茂
  • Organizer: 日本眼科学会
  • Place of Presentation: 東京
  • Year and Date: 2013-04-05
• [Presentation] Exome-wide association study for the identification of genes for primary open angle glaucoma (POAG) (2013)
  • Author(s): Li Z, Khor CC, Ikeda Y, Jia L, Chen LJ, Nakano M, GeorgeR, Do T, Abu-Amero, K, Tajudin LS, Kee C, Mineo O, Takanori M, Zhang M, Jonas JB, Chau T N, Fuse N, Wong TY, Liu JJ, Garway-Heath DF, Simmons CP, Vijaya L, Kinoshita S, Pang CP, Wang NL, Allingham RR, Hauser MA, Tashiro K, Aung T, Vithana EN
  • Organizer: 63rd Annual Meeting of the American Society of Human Genetics
  • Place of Presentation: Boston
• [Presentation] Evaluation of the Age-Related Speed of Anterior Chamber Reduction by 3D Scheimpflug Camera in Japanese Normal Subjects (2013)
  • Author(s): Ikeda Y , Mori K , Ueno M , Yoshikawa H, Maruyama Y , Yoshii K , Kinoshita S
  • Organizer: AAO
  • Place of Presentation: New Orleans
• [Presentation] Exome-wide association study for the identification of genes for primary open angle glaucoma (POAG) (2013)
  • Author(s): Li Z, Khor CC, Ikeda Y, Jia L, Chen LJ, Nakano M, GeorgeR, Do T, Abu-Amero, K, Tajudin LS, Kee C, Mineo O, Takanori M, Zhang M, Jonas JB, Chau T N, Fuse N, Wong TY, Liu JJ, Garway-Heath DF, Simmons CP, Vijaya L, Kinoshita S, Pang CP, Wang NL, Allingham RR, Hauser MA, Tashiro K, Aung T, Vithana EN.
  • Organizer: 63rd Annual Meeting of the American Society of Human Genetics,
  • Place of Presentation: Boston
• [Presentation] Evaluation of the Age-Related Speed of Anterior Chamber Reduction by 3D Scheimpflug Camera in Japanese Normal Subjects. (2013)
  • Author(s): Ikeda Y , Mori K , Ueno M , Yoshikawa H, Maruyama Y , Yoshii K , Kinoshita S.
  • Organizer: AAO
  • Place of Presentation: New Orleans
• [Presentation] 正常者におけるCDKN2B-AS1のジェノタイプ別臨床データの解析. (2013)
  • Author(s): 池田 陽子, 森 和彦, 上野 盛夫, 中野 正和, 吉井 健悟, 徳田 雄市, 大見 奈津江, 佐藤 隆一, 田代 啓, 木下 茂.
  • Organizer: 第117回日本眼科学会
  • Place of Presentation: 東京
• [Presentation] Common genetic variants of primary open-angle glaucoma in Japanese population. (2012)
  • Author(s): Nakano M, Ikeda Y, Tokuda Y, Fuwa M, Omi N, Adachi H, Ueno M, Mori K, Kinoshita S, and Tashiro K
  • Organizer: 62nd Annual Meeting of the American Society of Human Genetics
  • Place of Presentation: San Francisco
• [Presentation] Association of risk alleles of glaucoma marker SNPs with morphological characters of the optic disc (2012)
  • Author(s): Ikeda Y, Mori K, Ueno M, Imai K, Nakano M, Fuwa M, Yoshii K, Yagi Y, Tokuda Y, Tashiro K, and Kinoshita S
  • Organizer: 10th Congress of the European Glaucoma Society
  • Place of Presentation: Copenhagen
• [Presentation] Genome-wide association study on primary open-angle glaucoma with a 1000K gene chip (2012)
  • Author(s): Mori K, Ikeda Y, Ueno M, Imai K, Nakano M, Tokuda Y, Omi N, Adachi H, Tashiro K, and Kinoshita S
  • Organizer: Annual Meeting of the Association for Research in Vision and Ophthalmology
  • Place of Presentation: Florida
• [Presentation] Evaluation of Optic Disc Morphology with HRT-II of Middle-Age or Older Japanese Normal Subjects (2012)
  • Author(s): Ikeda Y, Mori K, Ueno M, Yoshikawa H, Maruyama Y, Kinoshita S
  • Organizer: AMERICAN ACADEMY OF OPHTHALMOLOGY
  • Place of Presentation: Chicago
• [Presentation] 眼科疾患と遺伝子異常.原発開放隅角緑内障関連バリアントとその領域の解析」 (2012)
  • Author(s): 池田陽子
  • Organizer: 第66回日本臨床眼科学会総会
  • Place of Presentation: 京都
• [Presentation] Seasonal Intraocular Pressure Variation in the Early Postoperative Phase of Trabeculectomy (2011)
  • Author(s): Ikeda Y, Mori K, Ueno M, Imai K
  • Organizer: American Academy of Ophthalmology
  • Place of Presentation: Orland
• [Presentation] Candidate Gene Analysis of Primary Open-Angle Glaucoma in a Japanese Population using a Custom Chip (2011)
  • Author(s): Ikeda Y, Mori K, Ueno M, Imai K, Fuwa F, Tokuda Yi, Nakano M, Yagi T, Tashiro K,Kinoshita S
  • Organizer: The Association for Reserch in Vision and Ophthalmology
  • Place of Presentation: Florida
• [Presentation] Candidate Gene Analysis of Primary Open-Angle Glaucoma in a Japanese Population using a Custom Chip (2011)
  • Author(s): Ikeda Y, Mori K, Ueno M, Imai K, Fuwa F, Tokuda Y, Nakano M, Yagi T, Tashiro K,Kinoshita S
  • Organizer: World Glaucoma Congress
  • Place of Presentation: Paris
• [Presentation] 正常者における緑内障疾患マーカーSNPと血液生化学データの関連性の検討. (2011)
  • Author(s): 池田陽子、吉井健悟、森 和彦、上野盛夫、中野正和、徳田雄市、大見奈津江、八木知人、今井浩二郎、田代啓、木下 茂.
  • Organizer: 第22回日本緑内障学会
  • Place of Presentation: 秋田
• [Presentation] 原発開放隅角緑内障関連遺伝子に対するカスタムチップ解析 (2011)
  • Author(s): 池田陽子、森 和彦、上野盛夫、今井浩二郎、不破正博、中野正和、谷口孝純、徳田雄市、大見奈津江、八木知人、田中雅深、田代啓、木下 茂
  • Organizer: 第115回日本眼科学会総会
  • Place of Presentation: 東京
• [Presentation] 加齢に伴う前房隅角形状変化の.齢別検討. (2011)
  • Author(s): 池田陽子、森 和彦、上野盛夫、今井浩二郎、木下 茂.
  • Organizer: 第11回.本抗加齢医学会総会
  • Place of Presentation: 京都
• [Presentation] Analysis of Ophthalmic Clinical Data Association for CDKN2B-AS1 Genotype in Normal Subjects.
  • Author(s): Ikeda Y, Mori K, Ueno M, Nakano M, Tokuda Y, Omi N, Sato R, Yoshii K, Tashiro; K, Kinoshita S.
  • Organizer: ARVO
  • Place of Presentation: Seattle
• [Presentation] 落屑緑内障患者における血液生化学的データの解析.
  • Author(s): 池田陽子, 森 和彦, 上野盛夫, 吉川晴菜, 加藤浩晃, 丸山悠子, 吉井健悟, 中野正和, 田代 啓, 木下 茂.
  • Organizer: 第24回日本緑内障学会
  • Place of Presentation: 東京
• [Presentation] 正常者前房隅角因子の加齢による減少スピードの検討.
  • Author(s): 池田陽子, 森 和彦, 上野盛夫, 吉川晴菜, 加藤浩晃, 丸山悠子, 木下 茂.
  • Organizer: 第67回日本臨床眼科学会.
  • Place of Presentation: 横浜
• [Book] 緑内障診療クローズアップ.緑内障診療の基本.緑内障に関連する遺伝子 (2014)
  • Author(s): 池田陽子、中野正和
  • Publisher: メジカルビュー
• [Book] 緑内障診療クローズアップ．緑内障診療の基本．緑内障に関連する遺伝子 (2014)
  • Author(s): 池田陽子、中野正和
  • Total Pages: 5
  • Publisher: メジカルビュー者
• [Book] All About開放隅角緑内障.開放隅角緑内障の遺伝要因と遺伝相談 (2013)
  • Author(s): 池田陽子、森和彦
  • Publisher: 医学書院
• [Book] All About 開放隅角緑内障 (2013)
  • Author(s): 池田陽子、森和彦
  • Publisher: 医学書院
• [Book] 線維柱帯除術 角膜移植後 (2012)
  • Author(s): 池田陽子、 森 和彦
  • Publisher: 文光堂
• [Book] 高眼圧の治療は、どうしたらよいでしょうか？専門医のための眼科診療クオリファイ緑内障薬物治療ガイド (2012)
  • Author(s): 吉川晴菜、池田陽子
  • Publisher: 中山書店
• [Book] 眼科手術６ 緑内障 線維柱帯切除術 角膜移植後 (2012)
  • Author(s): 池田陽子、森 和彦
  • Total Pages: 5
  • Publisher: 文光堂
• [Book] 専門医のための眼科診療クオリファイ緑内障診療ガイド.Goldmann視野計による診断の限界と意義 (2011)
  • Author(s): 上野盛夫、池田陽子
  • Total Pages: 5
  • Publisher: 中山書店