Project/Area Number |
12307020
|
Research Category |
Grant-in-Aid for Scientific Research (A)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Psychiatric science
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Research Institution | RIKEN |
Principal Investigator |
YOSHIKAWA Takeo RIKEN, Lab. for Molecular Psychiatry, Head, 分子精神科学研究チーム, チームリーダー (30249958)
|
Co-Investigator(Kenkyū-buntansha) |
ARINAMI Tadao University of Tsukuba, Dept. of Medical Genetics,Associate Professor, 基礎医学系, 助教授 (10212648)
YAMADA Kazuo RIKEN, Lab. for Molecular Psychiatry, Research Scientist, 分子精神科学研究チーム, 研究員 (10322695)
EBIHARA Mitsuru RIKEN, Lab. for Molecular Psychiatry, Research Scientist, 分子精神科学研究チーム, 研究員 (80232974)
菊池 美香 理化学研究所, 分子精神科学研究チーム, テクニカルスタッフ(研究職)
大野 真一 理化学研究所, 分子精神科学研究チーム, テクニカルスタッフ(研究職)
|
Project Period (FY) |
2000 – 2002
|
Project Status |
Completed (Fiscal Year 2002)
|
Budget Amount *help |
¥35,690,000 (Direct Cost: ¥33,800,000、Indirect Cost: ¥1,890,000)
Fiscal Year 2002: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2001: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Fiscal Year 2000: ¥27,500,000 (Direct Cost: ¥27,500,000)
|
Keywords | schizophrenia / pedigree / genome scan / family-based association / chromosome 11 / chromosome 18 / choline knase / C18orf1 / ETDT / ハプロタイプ / C18orf1 / SNP / マイクロサテライトマーカー / 内因性精神病 / 精神分裂病 / 感情病 / 全ゲノムassociation study / IMPA2遺伝子 / 学習性無力ラット / gene chip / 全ゲノムassociation scanning |
Research Abstract |
Family-based linkage disequilibrium (LD) mapping has been suggested as a powerful and practical alternative to linkage analysis. We have performed a genome-wide LD survey of susceptibility loci for schizophrenia in a Japanese population. We first typed 119 schizophrenic pedigrees (357 individuals) with 444 microsatellite markers, and analyzed the data using the pedigree disequilibrium test. This analysis revealed 14 markers that showed significant transmission distortion. To corroborate these findings, we changed our statistical methods to the extended transmission disequilibrium test (ETDT) , using 80 independent complete trios (a schizophrenic offspring and their parents), 68 of which were derived from the initial pedigrees and 12 newly recruited trios. ETDT supported two markers for continued association, D11S987 on 11q13.3 (P=0.00009) and D16S423 on 16p13.3 (P=0.002). We scrutinized the most significant genomic locus on 11q11-13 by adding 26 new markers for analysis. Results of three-marker haplotype analysis in the region showed evidence of association with schizophrenia (most significant haplotype P=0.0005, global P=0.022). Although the present study may have missed other potential genomic intervals because of the sparse mapping density, we hope that it has identified promising anchor points for further studies to identify risk-conferring genes in Japanese schizophrenia.
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