GENETIC STUDY OF SCHIZOPHRENIA IN AN ETHNIC MINORITY

少数民族精神分裂症的遗传学研究

基本信息

批准号：
2890686
负责人：
MARINA MYLES-WORSLEY
金额：
$ 19.69万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
1996
资助国家：
美国
起止时间：
1996-04-01 至 2001-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2890686
关键词：
Asians behavioral /social science research tag behavioral genetics clinical research evoked potentials family genetics genetic markers genotype human genetic material tag human subject linkage mapping mental disorder diagnosis phenotype psychophysiology schizophrenia smooth pursuit eye movement

项目摘要

DESCRIPTION (Adapted from the Applicant's Abstract): It is widely accepted that genetic transmission is of major etiological importance in the pathogenesis of schizophrenia. Consequently, there has been a major investment in linkage studies using multiplex families segregating schizophrenia, one of the best available methods for elucidating the genetics of complex disease. Unfortunately, schizophrenia, with its non- Mendelian transmission patterns, diagnostic uncertainly, reduced penetrance, phenocopies, and possible genetic heterogeneity, has proven to be a remarkably difficult disease to study with standard linkage techniques. The proposed project aims to search for major genes underlying schizophrenia using four strategies that can address the problems inherent in genetic linkage studies of schizophrenia. 1) With respect to families/subjects, the investigators propose to study exceptionally large multiplex clans in Palau, Micronesia where the population has been geographically and ethnically isolated from outside genetic influences, yet is not inbred. Given the large sibships found in these families, the large number of family members willing to participate, and the greater probability of genetic homogeneity across families in this geographic isolate, the power to detect linkage with these three families is equivalent to the power to detect linkage with 200 small-to medium-sized families. The investigators also plan to ascertain all cases of schizophrenia to be used for future linkage disequilibrium studies in areas of potential linkage found in the current project. 2) With respect to phenotyping, the investigators will phenotype the largest pedigrees using the standard diagnostic phenotype as well as two of the most promising endophenotypes for schizophrenia, SPEM and P50 sensory gating, which offer the advantages of higher penetrances and more clearly defined patterns of inheritance. 3) For genotyping these pedigrees, the investigators will be using a two-pronged approach, including polymorphic candidate genes or regions and a genome scan. 4) The data will be analyzed according to the following specific plans for each study. For Study 1, linkage analysis using the schizophrenia phenotype will be used to test the hypothesis that effects of a major gene contribute to schizophrenia. For Study 2, linkage analysis using psychophysiological endophenotypes will be used. The investigators will use disease status and the two endophenotypes to develop a composite quantitative phenotype which will represent liability for schizophrenia. They will then follow- up all positive results found in Study 1 using this more sensitive phenotype in quantitative linkage analysis.

描述（改编自申请人的摘要）：它被广泛承认遗传传播在病因学上具有重要意义精神分裂症的发病机制。因此，出现了重大的使用多重家族分离进行连锁研究的投资精神分裂症是阐明精神分裂症的最佳可用方法之一复杂疾病的遗传学。不幸的是，精神分裂症及其非孟德尔传播模式，诊断不确定性，减少外显率、表型和可能的遗传异质性已被证明是一种非常难以通过标准联系进行研究的疾病技术。拟议的项目旨在寻找潜在的主要基因精神分裂症使用四种策略可以解决问题精神分裂症遗传连锁研究中固有的。 1）尊重对于家庭/受试者，研究人员建议进行特殊研究密克罗尼西亚帕劳的大型复合氏族，那里的人口一直在在地理和种族上与外界遗传影响隔离，但不是近亲繁殖。鉴于这些家庭中存在大量的同胞关系，愿意参与的家庭成员数量较多，该地理区域内各家族遗传同质性的概率隔离，检测与这三个家族的联系的能力是相当于200个中小型检测联动的力量家庭。调查人员还计划查明所有案件精神分裂症将用于未来的连锁不平衡研究当前项目中发现的潜在联系领域。 2）尊重为了进行表型分析，研究人员将对最大的谱系进行表型分析使用标准诊断表型以及两种最常用的诊断表型精神分裂症、SPEM 和 P50 感觉门控的有希望的内表型，具有更高的外显率和更清晰的优点继承模式。 3）为了对这些谱系进行基因分型，研究人员将使用双管齐下的方法，包括多态性候选基因或区域以及基因组扫描。 4）数据将是根据以下每项研究的具体计划进行分析。为了研究1，将使用精神分裂症表型的连锁分析检验主要基因的影响有助于的假设精神分裂症。对于研究 2，使用心理生理学进行连锁分析将使用内表型。研究人员将使用疾病状态和两种内表型以开发复合定量表型这将代表精神分裂症的责任。然后他们将遵循—— 使用这种更敏感的方法，得出研究 1 中发现的所有阳性结果定量连锁分析中的表型。