Identification of susceptibility genes for functional psychoses by whole genome scan

全基因组扫描鉴定功能性精神病易感基因

基本信息

批准号：
12307020
负责人：
YOSHIKAWA Takeo
金额：
$ 22.84万
依托单位：
RIKEN
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

项目摘要

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.

基于家庭的连锁不平衡（LD）映射已被认为是链接分析的强大而实用的替代方法。我们已经对日本人群中精神分裂症的易感基因座进行了全基因组LD调查。我们首先键入119个具有444个微卫星标记的精神分裂症（357个个体），并使用谱系不平衡测试分析了数据。该分析揭示了14个标记，显示出明显的传输失真。为了证实这些发现，我们使用80个独立的完整三重奏（精神分裂后代和他们的父母）将统计方法更改为扩展的传输不平衡测试（ETDT），其中68个来自最初的谱系和12个新招募的三架。 ETDT支持了持续关联的两个标记，在11q13.3（p = 0.00009）和D16S423在16p13.3（p = 0.002）上支持了D11S987。我们通过添加26个新标记来分析，仔细研究了11q11-13上最重要的基因组基因座。该地区三标记单倍型分析的结果显示出与精神分裂症相关的证据（最显着的单倍型P = 0.0005，全局P = 0.022）。尽管本研究可能由于尺寸稀少而错过了其他潜在的基因组间隔，但我们希望它已经确定了进一步研究的有希望的锚点，以鉴定日本精神分裂症中的风险支配基因。