2-1.SNPタイピングセンター Human SNP Typing Center

We established Human SNP Typing Center in our department for the purpose of intensive SNP (single nucleotide polymorphism) analysis in multi‐institutional joint research.

<研究背景>

ヒト多因子疾患の疾患感受性遺伝子を同定するために、多施設共同研究が有効な手段となります。多施設共同研究における集約的なSNP(単一塩基多型)解析を目的として、当教室に「ヒトSNPタイピングセンター」を設置しました。

<研究のアプローチ>

*ゲノムワイド関連解析*

ヒト多因子疾患の疾患感受性遺伝子を探索する統計遺伝学的手法には、大別して連鎖分析と関連分析があります。連鎖分析は患者家族を対象として、文字通り疾患遺伝子と多型マーカーの連鎖を検出する手法であり、ゲノム全域に分布する1万から数万種類のSNPを用いれば十分です。一方、関連分析の代表であるケース・コントロール関連分析法は非血縁の患者群と健常対照群を対象として、疾患遺伝子と多型マーカーの連鎖不平衡を検出する手法であり、これをゲノム全域にわたって適用するゲノムワイド関連解析(GWAS)では数十万種類以上のSNPあるいは数万種以上のマイクロサテライトマーカーを解析することが必要となります。

現在市販されているキットを用いると、最大で500万種のSNPおよびCNVのゲノムワイド解析が可能です。ヒトSNPタイピングセンターではこのような解析を効率的に行うためのシステムを構築し、いくつかの多因子疾患についてゲノムワイド関連分析を実施しています。

候補遺伝子アプローチおよび候補領域の絞り込み

ゲノムワイド連鎖分析あるいはゲノムワイド関連分析によって検出された候補領域における網羅的SNP解析や、推定される発症機序に基づく候補遺伝子の網羅的SNP解析を行っています。数十から数百種類のSNPを解析対象とする場合には、当研究室で開発したDigiTag2法によりSNPタイピングを行い、また、一種類のSNPについて多検体を解析する場合にはTaqMan法によるSNPタイピングを実施しています。

<主な成果>

ヒトSNPタイピングセンターに最新のプラットフォームを導入し、192検体/週のペースで約60万種のSNPタイピングを行っています。これまでに420名の日本人健常者、およびパニック障害、肝炎などの疾患について合計15,000名の症例を対象としたゲノムワイドSNPタイピングを実施しました。また、2型糖尿病についても、ゲノムワイド関連分析後の大規模SNP解析による新規感受性遺伝子の同定に貢献しました。

<本研究に関する文献>

ゲノムワイド関連解析関連

  • Kawashima M, Hitomi Y, Aiba Y, Nishida N, Kojima K, Kawai Y, Nakamura H, Tanaka A, Zeniya M, Hashimoto E, Ohira H, Yamamoto K, Abe M, Nakao K, Yamagiwa S, Kaneko S, Honda M, Umemura T, Ichida T, Seike M, Sakisaka S, Harada M, Yokosuka O, Ueno Y, Senju M, Kanda T, Shibata H, Himoto T, Murata K, Miyake Y, Ebinuma H, Taniai M, Joshita S, Nikami T, Ota H, Kouno H, Kouno H, Nakamuta M, Fukushima N, Kohjima M, Komatsu T, Komeda T, Ohara Y, Muro T, Yamashita T, Yoshizawa K, Nakamura Y, Shimada M, Hirashima N, Sugi K, Ario K, Takesaki E, Naganuma A, Mano H, Yamashita H, Matsushita K, Yamauchi K, Makita F, Nishimura H, Furuta K, Takahashi N, Kikuchi M, Masaki N, Tanaka T, Tamura S, Mori A, Yagi S, Shirabe K, Komori A, Migita K, Ito M, Nagaoka S, Abiru S, Yatsuhashi H, Yasunami M, Shimoda S, Harada K, Egawa H, Maehara Y, Uemoto S, Kokudo N, Takikawa H, Ishibashi H, Chayama K, Mizokami M, Nagasaki M, Tokunaga K, Nakamura M. (2017) Genome-wide association studies identify PRKCB as a novel genetic susceptibility locus for primary biliary cholangitis in the Japanese population. Hum Mol Genet (in press)
  • Nagao Y, Nishida N, Toyo-Oka L, Kawaguchi A, Amoroso A, Carrozzo M, Sata M, Mizokami M, Tokunaga K, Tanaka Y. (2017) Genome-wide Association Study Identifies Risk Variants for Lichen Planus in Patients With Hepatitis C Virus Infection. Clin Gastroenterol Hepatol (in press)
  • Matsunami K, Nishida N, Kaneko N, Ikeo K, Toyo-Oka L, Takeuchi H, Matsuura K, Tamori A, Nomura H, Yoshiji H, Imamura M, Masaki N, Hayakawa T, Ide T, Shimada N, Ikeda F, Hino K, Nishiguchi S, Okuse C, Nojiri S, Sawamoto K, Tokunaga K, Joh T, Tanaka Y. (2016) Genome-Wide Association Study Identifies ZNF354C Variants Associated with Depression from Interferon-Based Therapy for Chronic Hepatitis C. PLoS One 11(10):e0164418.
  • Aiba Y, Yamazaki K, Nishida N, Kawashima M, Hitomi Y, Nakamura H, Komori A, Fuyuno Y, Takahashi A, Kawaguchi T, Takazoe M, Suzuki Y, Motoya S, Matsui T, Esaki M, Matsumoto T, Kubo M, Tokunaga K, Nakamura M. (2015) Disease susceptibility genes shared by primary biliary cirrhosis and Crohn's disease in the Japanese population. J Hum Genet 60(9):525-31.
  • Khor SS, Yang W, Kawashima M, Kamitsuji S, Zheng X, Nishida N, Sawai H, Toyoda H, Miyagawa T, Honda M, Kamatani N, Tokunaga K. (2015) High-accuracy imputation for HLA class I and II genes based on high-resolution SNP data of population-specific references. Pharmacogenomics J (in press)
  • Hitomi Y, Kawashima M, Aiba Y, Nishida N, Matsuhashi M, Okazaki H, Nakamura M, Tokunaga K. (2015) Human primary biliary cirrhosis-susceptible allele of rs4979462 enhances TNFSF15 expression by binding NF-1. Hum Genet 134(7):737-47.
  • Iio E, Matsuura K, Nishida N, Maekawa S, Enomoto N, Nakagawa M, Sakamoto N, Yatsuhashi H, Kurosaki M, Izumi N, Hiasa Y, Masaki N, Ide T, Hino K, Tamori A, Honda M, Kaneko S, Mochida S, Nomura H, Nishiguchi S, Okuse C, Itoh Y, Yoshiji H, Sakaida I, Yamamoto K, Watanabe H, Hige S, Matsumoto A, Tanaka E, Tokunaga K, Tanaka Y. (2015) Genome-wide association study identifies a PSMD3 variant associated with neutropenia in interferon-based therapy for chronic hepatitis C. Hum Genet 134(3):279-89.
  • Awata T, Yamashita H, Kurihara S, Morita-Ohkubo T, Miyashita Y, Katayama S, Mori K, Yoneya S, Kohda M, Okazaki Y, Maruyama T, Shimada A, Yasuda K, Nishida N, Tokunaga K, Koike A (2014) A genome-wide association study for diabetic retinopathy in a Japanese population: potential association with a long intergenic non-coding RNA. PLoS ONE 9(11):e111715.
  • Okada Y, Wu D, Trynka G, Raj T, Terao C, Ikari K, Kochi Y, Ohmura K, Suzuki A, Yoshida S, Graham RR, Manoharan A, Ortmann W, Bhangale T, Denny JC, Carroll RJ, Eyler AE, Greenberg JD, Kremer JM, Pappas DA, Jiang L, Yin J, Ye L, Su DF, Yang J, Xie G, Keystone E, Westra HJ, Esko T, Metspalu A, Zhou X, Gupta N, Mirel D, Stahl EA, Diogo D, Cui J, Liao K, Guo MH, Myouzen K, Kawaguchi T, Coenen MJ, van Riel PL, van de Laar MA, Guchelaar HJ, Huizinga TW, Dieudé P, Mariette X, Bridges SL Jr, Zhernakova A, Toes RE, Tak PP, Miceli-Richard C, Bang SY, Lee HS, Martin J, Gonzalez-Gay MA, Rodriguez-Rodriguez L, Rantapää-Dahlqvist S, Arlestig L, Choi HK, Kamatani Y, Galan P, Lathrop M; RACI consortium; GARNET consortium, Eyre S, Bowes J, Barton A, de Vries N, Moreland LW, Criswell LA, Karlson EW, Taniguchi A, Yamada R, Kubo M, Liu JS, Bae SC, Worthington J, Padyukov L, Klareskog L, Gregersen PK, Raychaudhuri S, Stranger BE, De Jager PL, Franke L, Visscher PM, Brown MA, Yamanaka H, Mimori T, Takahashi A, Xu H, Behrens TW, Siminovitch KA, Momohara S, Matsuda F, Yamamoto K, Plenge RM (2014) Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature 506(7488):376-81.
  • Nishida N, Tokunaga K, Mizokami M (2014) Genome-Wide Association Study Reveals Host Genetic Factors for Liver Diseases. Journal of Clinical and Translational Hepatology (in press)
  • Nishida N, Sawai H, Kashiwase K, Minami M, Sugiyama M, Seto WK, Yuen MF, Posuwan N, Poovorawan Y, Ahn SH, Han KH, Matsuura K, Tanaka Y, Kurosaki M, Mizokami M (2014) New susceptibility and resistance HLA-DP alleles to HBV-related diseases identified by a trans-ethnic association study in Asia. PLoS One 9(2):e86449.
  • Kanazawa T, Ikeda M, Glatt SJ, Tsutsumi A, Kikuyama H, Kawamura Y, Nishida N, Miyagawa T, Hashimoto R, Takeda M, Sasaki T, Tokunaga K, Koh J, Iwata N, Yoneda H (2013) Genome-wide association study of atypical psychosis. Am J Med Genet B Neuropsychiatr Genet 1628(7):679-86.
  • Miyashita A, Koike A, Jun G, Wang LS, Takahashi S, Matsubara E, Kawarabayashi T, Shoji M, Tomita N, Arai H, Asada T, Harigaya Y, Ikeda M, Amari M, Hanyu H, Higuchi S, Ikeuchi T, Nishizawa M, Suga M, Kawase Y, Akatsu H, Kosaka K, Yamamoto T, Imagawa M, Hamaguchi T, Yamada M, Moriaha T, Takeda M, Takao T, Nakata K, Fujisawa Y, Sasaki K, Watanabe K, Nakashima K, Urakami K, Ooya T, Takahashi M, Yuzuriha T, Serikawa K, Yoshimoto S, Nakagawa R, Kim JW, Ki CS, Won HH, Na DL, Seo SW, Mook-Jung I, St George-Hyslop P, Mayeux R, Haines JL, Pericak-Vance MA, Yoshida M, Nishida N, Tokunaga K, Yamamoto K, Tsuji S, Kanazawa I, Ihara Y, Schellenberg GD, Farrer LA, Kuwano R (2013) SORL1 Is Genetically Associated with Late-Onset Alzheimer's Disease in Japanese, Koreans and Caucasians. PLoS One 8(4):e58618.
  • Kawamura Y, Takahashi T, Liu X, Nishida N, Tokunaga K, Ukawa K, Noda Y, Yoshikawa A, Shimada T, Umekage T, Sasak T (2013) DNA polymorphism in the FKBP5 gene affects impulsivity in intertemporal choice. Asia Pac Psychiatry 5(1):31-8.
  • Nakamura M, Nishida N, Kawashima M, Aiba Y, Tanaka A, Yasunami M, Nakamura H, Komori A, Nakamuta M, Zeniya M, Hashimoto E, Ohira H, Yamamoto K, Onji M, Kaneko S, Honda M, Yamagiwa S, Nakao K, Ichida T, Takikawa H, Seike M, Umemura T, Ueno Y, Sakisaka S, Kikuchi K, Ebinuma H, Yamashiki N, Tamura S, Sugawara Y, Mori A, Yagi S, Shirabe K, Taketomi A, Arai K, Monoe K, Ichikawa T, Taniai M, Miyake Y, Kumagi T, Abe M, Yoshizawa K, Joshita S, Shimoda S, Honda K, Takahashi H, Hirano K, Takeyama Y, Harada K, Migita K, Ito M, Yatsuhashi H, Fukushima N, Ota H, Komatsu T, Saoshiro T, Ishida J, Kouno H, Yagura M, Kobayashi M, Muro T, Masaki N, Hirata K, Watanabe Y, Nakamura Y, Shimada M, Hirashima N, Komeda T, Sugi K, Koga M, Ario K, Takesaki E, Maehara Y, Uemoto S, Kokudo N, Tsubouchi H, Mizokami M, Nakanuma Y, Tokunaga K, Ishibashi H (2012) Genome-wide Association Study Identifies TNFSF15 and POU2AF1 as Susceptibility Loci for Primary Biliary Cirrhosis in the Japanese Population. Am J Hum Genet 91(4):721-8.
  • Nishida N, Sawai H, Matsuura K, Sugiyama M, Ahn SH, Park JY, Hige S, Kang JH, Suzuki K, Kurosaki M, Asahina Y, Mochida S, Watanabe M, Tanaka E, Honda M, Kaneko S, Orito E, Itoh Y, Mita E, Tamori A, Murawaki Y, Hiasa Y, Sakaida I, Korenaga M, Hino K, Ide T, Kawashima M, Mawatari Y, Sageshima M, Ogasawara Y, Koike A, Izumi N, Han KH, Tanaka Y, Tokunaga K, Mizokami M (2012) Genome-Wide Association Study Confirming Association of HLA-DP with Protection against Chronic Hepatitis B and Viral Clearance in Japanese and Korean. PLoS One 7(6):e39175.
  • Okada Y, Terao C, Ikari K, Kochi Y, Ohmura K, Suzuki A, Kawaguchi T, Stahl EA, Kurreeman FA, Nishida N, Ohmiya H, Myouzen K, Takahashi M, Sawada T, Nishioka Y, Yukioka M, Matsubara T, Wakitani S, Teshima R, Tohma S, Takasugi K, Shimada K, Murasawa A, Honjo S, Matsuo K, Tanaka H, Tajima K, Suzuki T, Iwamoto T, Kawamura Y, Tanii H, Okazaki Y, Sasaki T, Gregersen PK, Padyukov L, Worthington J, Siminovitch KA, Lathrop M, Taniguchi A, Takahashi A, Tokunaga K, Kubo M, Nakamura Y, Kamatani N, Mimori T, Plenge RM, Yamanaka H, Momohara S, Yamada R, Matsuda F, Yamamoto K (2012) Meta-analysis identifies nine new loci associated with rheumatoid arthritis in the Japanese population. Nat Genet 44(5):511-6.
  • Hirata M, Kugimiya F, Fukai A, Saito T, Yano F, Ikeda T, Mabuchi A, Sapkota BR, Akune T, Nishida N, Yoshimura N, Nakagawa T, Tokunaga K, Nakamura K, Chung UI, Kawaguchi H (2012) C/EBPbeta and RUNX2 cooperate to degrade cartilage with MMP-13 as the target and HIF-2alpha as the inducer in chondrocytes. Hum Mol Genet 21(5):1111-23.
  • Kawamura Y, Otowa T, Koike A, Sugaya N, Yoshida E, Yasuda S, Inoue K, Takei K, Konishi Y, Tanii H, Shimada T, Tochigi M, Kakiuchi C, Umekage T, Liu X, Nishida N, Tokunaga K, Kuwano R, Okazaki Y, Kaiya H, Sasaki T (2011) A genome-wide CNV association study on panic disorder in a Japanese population. J Hum Genet 56(12):852-6.
  • Tanaka Y, Kurosaki M, Nishida N, Sugiyama M, Matsuura K, Sakamoto N, Enomoto N, Yatsuhashi H, Nishiguchi S, Hino K, Hige S, Itoh Y, Tanaka E, Mochida S, Honda M, Hiasa Y, Koike A, Sugauchi F, Kaneko S, Izumi N, Tokunaga K, Mizokami M (2011) Genome-wide association study identified ITPA/DDRGK1 variants reflecting thrombocytopenia in pegylated interferon and ribavirin therapy for chronic hepatitis C. Hum Mol Genet 20(17):3507-16.
  • Sakamoto N, Nakagawa M, Tanaka Y, Sekine-Osajima Y, Ueyama M, Kurosaki M, Nishida N, Tamori A, Yuki NS, Itsui Y, Azuma S, Kakinuma S, Hige S, Itoh Y, Tanaka E, Hiasa Y, Izumi N, Tokunaga K, Mizokami M, Watanabe M (2011) Association of IL28B variants with response to pegylated-interferon alpha plus ribavirin combination therapy reveals intersubgenotypic differences between genotypes 2a and 2b. J Med Virol 83(5):871-8.
  • Otowa T, Kawamura Y, Sugaya N, Yoshida E, Shimada T, Liu X, Tochigi M, Umekage T, Miyagawa T, Nishida N, Kaiya H, Okazaki Y, Tokunaga K, Sasaki T (2011) Association study of PDE4B with panic disorder in the Japanese population. Prog Neuropsychopharmacol Biol Psychiatry 35(2):545-9.
  • Kurosaki M, Tanaka Y, Nishida N, Sakamoto N, Enomoto N, Honda M, Sugiyama M, Matsuura K, Sugauchi F, Asahina Y, Nakagawa M, Watanabe M, Sakamoto M, Maekawa S, Sakai A, Kaneko S, Ito K, Masaki N, Tokunaga K, Izumi N, Mizokami M (2011) Pre-treatment prediction of response to pegylated-interferon plus ribavirin for chronic hepatitis C using genetic polymorphism in IL28B and viral factors. J Hepatol 54(3):439-48.
  • Evangelou E, Valdes AM, Kerkhof HJ, Styrkarsdottir U, Zhu Y, Meulenbelt I, Lories RJ, Karassa FB, Tylzanowski P, Bos SD, Akune T, Arden NK, Carr A, Chapman K, Cupples LA, Dai J, Deloukas P, Doherty M, Doherty S, Engstrom G, Gonzalez A, Halldorsson BV, Hammond CL, Hart DJ, Helgadottir H, Hofman A, Ikegawa S, Ingvarsson T, Jiang Q, Jonsson H, Kaprio J, Kawaguchi H, Kisand K, Kloppenburg M, Kujala UM, Lohmander LS, Loughlin J, Luyten FP, Mabuchi A, McCaskie A, Nakajima M, Nilsson PM, Nishida N, Ollier WE, Panoutsopoulou K, van de Putte T, Ralston SH, Rivadeneira F, Saarela J, Schulte-Merker S, Shi D, Slagboom PE, Sudo A, Tamm A, Tamm A, Thorleifsson G, Thorsteinsdottir U, Tsezou A, Wallis GA, Wilkinson JM, Yoshimura N, Zeggini E, Zhai G, Zhang F, Jonsdottir I, Uitterlinden AG, Felson DT, van Meurs JB, Stefansson K, Ioannidis JP, Spector TD (2011) Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22. Ann Rheum Dis 70(2):349-55.
  • Adachi S, Tajima A, Quan J, Haino K, Yoshihara K, Masuzaki H, Katabuchi H, Ikuma K, Suginami H, Nishida N, Kuwano R, Okazaki Y, Kawamura Y, Sasaki T, Tokunaga K, Inoue I, Tanaka K (2010) Meta-analysis of genome-wide association scans for genetic susceptibility to endometriosis in Japanese population. J Hum Genet 55(12):816-21.
  • Sakamoto N, Tanaka Y, Nakagawa M, Yatsuhashi H, Nishiguchi S, Enomoto N, Azuma S, Nishimura-Sakurai Y, Kakinuma S, Nishida N, Tokunaga K, Honda M, Ito K, Mizokami M, Watanabe M (2010) ITPA gene variant protects against anemia induced by pegylated interferon-alpha and ribavirin therapy for Japanese patients with chronic hepatitis C. Hepatol Res 40(11):1063-71.
  • Saito T, Fukai A, Mabuchi A, Ikeda T, Yano F, Ohba S, Nishida N, Akune T, Yoshimura N, Nakagawa T, Nakamura K, Tokunaga K, Chung UI, Kawaguchi H (2010) Transcriptional regulation of endochondral ossification by HIF-2alpha during skeletal growth and osteoarthritis development. Nat Med 16(6):678-86.
  • Otowa T, Tanii H, Sugaya N, Yoshida E, Inoue K, Yasuda S, Shimada T, Kawamura Y, Tochigi M, Minato T, Umekage T, Miyagawa T, Nishida N, Tokunaga K, Okazaki Y, Kaiya H, Sasaki T (2010) Replication of a genome-wide association study of panic disorder in a Japanese population. J Hum Genet: 55(2):91-6.
  • Tanaka Y, Nishida N, Sugiyama M, Kurosaki M, Matsuura K, Sakamoto N, Nakagawa M, Korenaga M, Hino K, Hige S, Ito Y, Mita E, Tanaka E, Mochida S, Murawaki Y, Honda M, Sakai A, Hiasa Y, Nishiguchi S, Koike A, Sakaida I, Imamura M, Ito K, Yano K, Masaki N, Sugauchi F, Izumi N, Tokunaga K, Mizokami M (2009) Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C. Nature Genetics 41(10):1105-9.
  • Koike A, Nishida N, Inoue I, Tsuji S, Tokunaga K (2009) Genome-wide association database developed in the Japanese Integrated Database Project. Journal of Human Genetics 54(9):543-6.
  • Otowa T, Yoshida E, Sugaya N, Yasuda S, Nishimura Y, Inoue K, Tochigi M, Umekage T, Miyagawa T, Nishida N, Tokunaga K, Tanii H, Sasaki T, Kaiya H, Okazaki Y (2009) Genome-wide association study of panic disorder in the Japanese population. Journal of Human Genetics 54(2):122-126
  • Horikawa Y, Miyake K, Yasuda K, Enya M, Hirota Y, Yamagata K, Hinokio Y, Oka Y, Iwasaki N, Iwamoto Y, Yamada Y, Seino Y, Maegawa H, Kashiwagi A, Yamamoto K, Tokunaga K, Takeda J, Kasuga M (2008) Replication of genome-wide association studies of type 2 diabetes susceptibility in Japan. The Journal of clinical endocrinology and metabolism 93(8):3136-3141
  • Yasuda K, Miyake K, Horikawa Y, Hara K, Osawa H, Furuta H, Hirota Y, Mori H, Jonsson A, Sato Y, Yamagata K, Hinokio Y, Wang HY, Tanahashi T, Nakamura N, Oka Y, Iwasaki N, Iwamoto Y, Yamada Y, Seino Y, Maegawa H, Kashiwagi A, Takeda J, Maeda E, Shin HD, Cho YM, Park KS, Lee HK, Ng MC, Ma RC, So WY, Chan JC, Lyssenko V, Tuomi T, Nilsson P, Groop L, Kamatani N, Sekine A, Nakamura Y, Yamamoto K, Yoshida T, Tokunaga K, Itakura M, Makino H, Nanjo K, Kadowaki T, Kasuga M (2008) Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus. Nature Genetics 40(9):1092-1097
  • Mahasirimongkol S, Yanai H, Nishida N, Ridruechai C, Matsushita I, Ohashi J, Summanapan S, Yamada N, Moolphate S, Chuchotaworn C, Chaiprasert A, Manosuthi W, Kantipong P, Kanitwittaya S, Sura T, Khusmith S, Tokunaga K, Sawanpanyalert P, Keicho N (2009) Genome-wide SNP-based linkage analysis of tuberculosis in Thais. Genes and immunity 10:77-83
  • Nishida N, Koike A, Tajima A, Ogasawara Y, Ishibashi Y, Uehara Y, Inoue I, Tokunaga K (2008) Evaluating the performance of Affymetrix SNP Array 6.0 platform with 400 Japanese individuals. BMC Genomics 9(1):431
  • Miyagawa T, Kawashima M, Nishida N, Ohashi J, Kimura R, Fujimoto A, Shimada M, Morishita S, Shigeta T, Lin L, Hong SC, Faraco J, Shin YK, Jeong JH, Okazaki Y, Tsuji S, Honda M, Honda Y, Mignot E, Tokunaga K (2008) Variant between CPT1B and CHKB associated with susceptibility to narcolepsy. Nature Genetics 40(11):1324-1328
  • Miyagawa T, Nishida N, Ohashi J, Kimura R, Fujimoto A, Kawashima M, Koike A, Sasaki T, Tanii H, Otowa T, Momose Y, Nakahara Y, Gotoh J, Okazaki Y, Tsuji S, Tokunaga K (2008) Appropriate data cleaning methods for genome-wide association study. Journal of Human Genetics 53(10):886-893
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  • 小池麻子、西田奈央、徳永勝士 (2008) ゲノムワイド関連解析データベースの開発. 蛋白核酸酵素. 53(7):882-887
  • 西田奈央、徳永勝士 (2008) ゲノムワイドSNPタイピング技術の現状と将来. 医学のあゆみ. 225(9):721-725
  • 西田奈央、徳永勝士 (2008) ゲノムワイド関連分析による多因子疾患遺伝子の探索. 肝疾患 Review2008~2009: 85-91
  • 西田奈央、徳永勝士 (2007) 大規模SNPタイピングによる多因子疾患遺伝子の探索. 実験医学. 25(2):62-68

候補遺伝子アプローチおよび候補領域の絞り込み

  • Trinks J, Nishida N, Hulaniuk ML, Caputo M, Tsuchiura T, Marciano S, Haddad L, Blejer J, Bartoli S, Ameigeiras B, Frías SE, Vistarini C, Heinrich F, Remondegui C, Ceballos S, Echenique G, Charre Samman M, D'Amico C, Rojas A, Martínez A, Ridruejo E, Fernández RJ, Pratx LB, Salamone H, Nuñez F, Galdame O, Gadano A, Corach D, Sugiyama M, Flichman D, Tokunaga K, Mizokami M. (2017) Role of HLA-DP and HLA-DQ on the clearance of hepatitis B virus and the risk of chronic infection in a multiethnic population. Liver Int (in press)
  • Murata K, Asano M, Matsumoto A, Sugiyama M, Nishida N, Tanaka E, Inoue T, Sakamoto M, Enomoto N, Shirasaki T, Honda M, Kaneko S, Gatanaga H, Oka S, Kawamura YI, Dohi T, Shuno Y, Yano H, Mizokami M. (2016) Induction of IFN-λ3 as an additional effect of nucleotide, not nucleoside, analogues: a new potential target for HBV infection. Gut (in press)
  • Nishida N, Ohashi J, Khor SS, Sugiyama M, Tsuchiura T, Sawai H, Hino K, Honda M, Kaneko S, Yatsuhashi H, Yokosuka O, Koike K, Kurosaki M, Izumi N, Korenaga M, Kang JH, Tanaka E, Taketomi A, Eguchi Y, Sakamoto N, Yamamoto K, Tamori A, Sakaida I, Hige S, Itoh Y, Mochida S, Mita E, Takikawa Y, Ide T, Hiasa Y, Kojima H, Yamamoto K, Nakamura M, Saji H, Sasazuki T, Kanto T, Tokunaga K, Mizokami M. (2016) Understanding of HLA-conferred susceptibility to chronic hepatitis B infection requires HLA genotyping-based association analysis. Sci Rep 6:24767.
  • Nishida N, Ohashi J, Sugiyama M, Tsuchiura T, Yamamoto K, Hino K, Honda M, Kaneko S, Yatsuhashi H, Koike K, Yokosuka O, Tanaka E, Taketomi A, Kurosaki M, Izumi N, Sakamoto N, Eguchi Y, Sasazuki T, Tokunaga K, Mizokami M. (2015) Effects of HLA-DPB1 genotypes on chronic hepatitis B infection in Japanese. Tissue Antigens 86(6):406-12
  • Ueyama M, Nishida N, Korenaga M, Korenaga K, Kumagai E, Yanai H, Adachi H, Katsuyama H, Moriyama S, Hamasaki H, Sako A, Sugiyama M, Aoki Y, Imamura M, Murata K, Masaki N, Kawaguchi T, Torimura T, Hyogo H, Aikata H, Ito K, Sumida Y, Kanazawa A, Watada H, Okamoto K, Honda K, Kon K, Kanto T, Mizokami M, Watanabe S. (2015) The impact of PNPLA3 and JAZF1 on hepatocellular carcinoma in non-viral hepatitis patients with type 2 diabetes mellitus. J Gastroenterol 51(4):370-9
  • Ikeda M, Yoshimura R, Hashimoto R, Kondo K, Saito T, Shimasaki A, Ohi K, Tochigi M, Kawamura Y, Nishida N, Miyagawa T, Sasaki T, Tokunaga K, Kasai K, Takeda M, Nakamura J, Ozaki N, Iwata N (2015) Genetic Overlap Between Antipsychotic Response and Susceptibility to Schizophrenia. J Clin Psychopharmacol 35(1):85-8.
  • Srilohasin P, Chaiprasert A, Tokunaga K, Nishida N, Prammananan T, Smittipat N, Mahasirimongkol S, Chaiyasirinroje B, Yanai H, Palittapongarnpim P (2014) Genetic Diversity and Dynamic Distribution of Mycobacterium Tuberculosis Causing Pulmonary and Extra-Pulmonary Tuberculosis in Thailand. J Clin Microbiol 52(12):4267-74.
  • Kawasaki A, Furukawa H, Nishida N, Warabi E, Kondo Y, Ito S, Matsumoto I, Kusaoi M, Amano H, Suda A, Nagaoka S, Setoguchi K, Nagai T, Hirohata S, Shimada K, Sugii S, Okamoto A, Chiba N, Suematsu E, Ohno S, Katayama M, Okamoto A, Kono H, Tokunaga K, Takasaki Y, Hashimoto H, Sumida T, Tohma S, Tsuchiya N (2014) Association of Functional Polymorphisms in Interferon Regulatory Factor 2 (IRF2) with Susceptibility to Systemic Lupus Erythematosus: A Case-Control Association Study. PLoS One 9(10):e109764.
  • Nishino J, Sugiyama M, Nishida N, Tokunaga K, Mizokami M, Mano S (2014) The interaction of a single-nucleotide polymorphism with age on response to interferon-α and ribavirin therapy in female patients with hepatitis C infection. J Med Virol 86(7):1130-3.
  • Khudayberganova D, Sugiyama M, Masaki N, Nishida N, Mukaide M, Sekler D, Latipov R, Nataliya K, Dildora S, Sharapov S, Usmanova G, Raxmanov M, Musabaev E, Mizokami M (2014) IL28B Polymorphisms and Clinical Implications for Hepatitis C Virus Infection in Uzbekistan. PLoS One 9(3):e93011.
  • Aiba Y, Harada K, Komori A, Ito M, Shimoda S, Nakamura H, Nagaoka S, Abiru S, Migita K, Ishibashi H, Nakanuma Y, Nishida N, Kawashima M, Tokunaga K, Yatsuhashi H, Nakamura M (2014) Systemic and local expression levels of TNF-like ligand 1A and its decoy receptor 3 are increased in primary biliary cirrhosis. Liver Int 34(5):679-88.
  • Naka I, Hikami K, Nakayama K, Koga M, Nishida N, Kimura R, Furusawa T, Natsuhara K, Yamauchi T, Nakazawa M, Ataka Y, Ishida T, Inaoka T, Iwamoto S, Matsumura Y, Ohtsuka R, Tsuchiya N, Ohashi J (2013) A functional SNP upstream of the beta-2 adrenergic receptor gene (ADRB2) is associated with obesity in Oceanic populations. Int J Obes (Lond) 37(9):1204-10.
  • Oda K, Uto H, Kumagai K, Ido A, Kusumoto K, Shimoda K, Hayashi K, Stuver SO, Tanaka Y, Nishida N, Tokunaga K, Tsubouchi H. (2014) Impact of a single nucleotide polymorphism upstream of the IL28B gene in patients positive for anti-HCV antibody in an HCV hyperendemic area in Japan. J Med Virol 86(11):1877-85
  • Nishino J, Sugiyama M, Nishida N, Tokunaga K, Mizokami M, Mano S. (2014) The interaction of a single-nucleotide polymorphism with age on response to interferon-α and ribavirin therapy in female patients with hepatitis C infection. J Med Virol 86(7):1130-3.
  • Khudayberganova D, Sugiyama M, Masaki N, Nishida N, Mukaide M, Sekler D, Latipov R, Nataliya K, Dildora S, Sharapov S, Usmanova G, Raxmanov M, Musabaev E, Mizokami M. (2014) IL28B Polymorphisms and Clinical Implications for Hepatitis C Virus Infection in Uzbekistan. PLoS One 9(3):e93011.
  • Awata T, Yamashita H, Kurihara S, Morita-Ohkubo T, Miyashita Y, Katayama S, Kawasaki E, Tanaka S, Ikegami H, Maruyama T, Shimada A, Takahashi K, Kawabata Y, Kobayashi T, Nishida N, Mawatari Y (2013) A low-frequency GLIS3 variant associated with resistance to Japanese type 1 diabetes. Biochem Biophys Res Commun 437(4):521-5.
  • Sawai H, Nishida N, Mbarek H, Matsuda K, Mawatari Y, Yamaoka M, Hige S, Kang JH, Abe K, Mochida S, Watanabe M, Kurosaki M, Asahina Y, Izumi N, Honda M, Kaneko S, Tanaka E, Matsuura K, Itoh Y, Mita E, Korenaga M, Hino K, Murawaki Y, Hiasa Y, Ide T, Ito K, Sugiyama M, Ahn SH, Han KH, Park JY, Yuen MF, Nakamura Y, Tanaka Y, Mizokami M, Tokunaga K (2012) No association for Chinese HBV-related hepatocellular carcinoma susceptibility SNP in other East Asian populations. BMC Med Genet 13:47.
  • Naka I, Nishida N, Ohashi J (2011) No Evidence for Strong Recent Positive Selection Favoring the 7 Repeat Allele of VNTR in the DRD4 Gene. PLoS One 6(8):e24410.
  • Furusawa T, Naka I, Yamauchi T, Natsuhara K, Kimura R, Nakazawa M, Ishida T, Nishida N, Eddie R, Ohtsuka R, Ohashi J (2011) The serum leptin level and body mass index in Melanesian and Micronesian Solomon Islanders: focus on genetic factors and urbanization. Am J Hum Biol 23(4):435-44.
  • Okamoto K, Tokunaga K, Doi K, Fujita T, Suzuki H, Katoh T, Watanabe T, Nishida N, Mabuchi A, Takahashi A, Kubo M, Maeda S, Nakamura Y, Noiri E (2011) Common variation in GPC5 is associated with acquired nephrotic syndrome. Nat Genet 43(5):459-63.
  • Ridruechai C, Mahasirimongkol S, Phromjai J, Yanai H, Nishida N, Matsushita I, Ohashi J, Yamada N, Moolphate S, Summanapan S, Chuchottaworn C, Manosuthi W, Kantipong P, Kanitvittaya S, Sawanpanyalert P, Keicho N, Khusmith S, Tokunaga K (2010) Association analysis of susceptibility candidate region on chromosome 5q31 for tuberculosis. Genes Immun 11(5):416-22.
  • Furusawa T, Naka I, Yamauchi T, Natsuhara K, Kimura R, Nakazawa M, Ishida T, Inaoka T, Matsumura Y, Ataka Y, Nishida N, Tsuchiya N, Ohtsuka R, Ohashi J (2010) The Q223R polymorphism in LEPR is associated with obesity in Pacific Islanders. Hum Genet 127(3):287-94.
  • Naka I, Nishida N, Patarapotikul J, Nuchnoi P, Tokunaga K, Hananantachai H, Tsuchiya N, Ohashi J (2009) Identification of a haplotype block in the 5q31 cytokine gene cluster associated with the susceptibility to severe malaria. Malaria Journal 8:232.
  • Fujimoto A, Nishida N, Kimura R, Miyagawa T, Yuliwulandari R, Batubara L, Mustofa MS, Samakkarn U, Settheetham-Ishida W, Ishida T, Morishita Y, Tsunoda T, Tokunaga K, Ohashi J (2009) FGFR2 is associated with hair thickness in Asian populations. Journal of Human Genetics 54(8):461-5.
  • Fujimoto A, Ohashi J, Nishida N, Miyagawa T, Morishita Y, Tsunoda T, Kimura R, Tokunaga K (2008) A replication study confirmed the EDAR gene to be a major contributor to population differentiation regarding head hair thickness in Asia. Human Genetics 124(2):179-85.
  • Nuchnoi P, Ohashi J, Naka I, Nacapunchai D, Tokunaga K, Nishida N, Patarapotikul J (2008) Linkage disequilibrium structure of the 5q31-33 region in a Thai population. Journal of Human Genetics 53(9):850-6.
  • Yuliwulandari R, Sachrowardi Q, Nishida N, Takasu M, Batubara L, Susmiarsih TP, Rochani JT, Wikaningrum R, Miyashita R, Miyagawa T, Sofro AS, Tokunaga K (2008) Polymorphisms of promoter and coding regions of the arylamine N-acetyltransferase 2 (NAT2) gene in the Indonesian population: proposal for a new nomenclature. Journal of Human Genetics 53(3):201-9.
  • Nishida N, Tanabe T, Takasu M, Suyama A, Tokunaga K (2007) Further development of multiplex single nucleotide polymorphism typing method, the DigiTag2 assay. Analytical biochemistry 364(1):78-85
  • Noguchi E, Ohtsuki Y, Tokunaga K, Yamaoka-Sageshima M, Ichikawa K, Aoki T, Shibasaki M, Arinami T (2006) ADAM33 polymorphisms are associated with asthma susceptibility in a Japanese population. Clinical and experimental allergy 36(5): 602-608
  • Hara K, Horikoshi M, Kitazato H, Ito C, Noda M, Ohashi J, Froguel P, Tokunaga K, Tobe K, Nagai R, Kadowaki T (2006) Hepatocyte nuclear factor-4alpha P2 promoter haplotypes are associated with type 2 diabetes in the Japanese population. Diabetes 55(5):1260-1264
  • Nishida N, Tanabe T, Hashido K, Hirayasu K, Takasu M, Suyama A, Tokunaga K (2005) DigiTag assay for multiplex single nucleotide polymorphism typing with high success rate. Analytical biochemistry 346(2):281-288
  • Kent Doi, Hitomi Doi, Eisei Noiri, Akihide Nakao, Toshiro Fujita, Katsushi Tokunaga (2004) High-throughput single nucleotide polymorphism typing by fluorescent single-strand conformation polymorphism analysis with capillary electrophoresis. Electrophoresis 25:833-838
  • Bannai M, Higuchi K, Akesaka T, Furukawa M, Yamaoka M, Sato K, Tokunaga K (2004) Single-nucleotide-polymorphism genotyping for whole-genome-amplified samples using automated fluorescence correlation spectroscopy. Analytical biochemistry 327(2):215-221
  • 西田奈央、田邊哲也、高須美和、陶山明、徳永勝士 (2007) DigiTag2法によるマルチプレックスSNPタイピング. DNA多型 DNA POLYMORPHISM. 15:256-259
  • 西田奈央、平安恒幸、高須美和、陶山明、徳永勝士 (2006) DigiTag法を用いたマルチプレックスSNPタイピング. DNA多型 DNA POLYMORPHISM. 14:18-21
  • 西田奈央、平安恒幸、高須美和、陶山明、徳永勝士 (2005) DNAコンピューティングの原理に基づく新規SNPタイピング法の開発. DNA多型 DNA POLYMORPHISM. 13:14-16
  • 西田奈央、徳永勝士 (2004) プライマーエクステンションを用いたSNP解析, ゲノム研究実験ハンドブック 139-144

(文責:西田 奈央)

研究内容・設備

1.疾患関連研究
(Genetics and complex human diseases)

2.ヒトゲノムDNA解析システム
(Human Genome DNA analysis system)

3.データベース・解析ツール
(Database and analysis tool)

4.日本人健常者の全ゲノム多型・配列解析データの提供方針
(Data sharing policy of whole-genome polymorphism/sequence data of Japanese healthy individuals)