GENETIC STUDY OF SCHIZOPHRENIA IN AN ETHNIC MINORITY

少数民族精神分裂症的遗传学研究

• 批准号: 2675337
• 负责人: MARINA MYLES-WORSLEY
• 金额: $ 18.94万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 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/2675337
• 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

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）： 接受遗传传播是主要的病因学的重要性， 精神分裂症的发病机制 因此，有一个主要的 利用多重家系分离进行连锁研究的投资 精神分裂症，最好的方法之一，用于阐明 复杂疾病的遗传学 不幸的是，精神分裂症，其非- 孟德尔传播模式，诊断不确定性，降低 表型复制和可能的遗传异质性，已经证明 是一种非常难用标准连锁研究的疾病 技术. 该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)相对 对于家庭/受试者，研究者建议例外地研究 在密克罗尼西亚的帕劳，人口已经 在地理上和种族上与外界遗传影响隔绝， 但不是近亲繁殖的。 考虑到这些家庭中存在大量的兄弟姐妹关系， 许多家庭成员愿意参加，而且人数越多， 在这个地理区域内，各家族间的遗传同质性概率 分离，检测与这三个家庭的联系的能力是 相当于检测200个中小型 家庭 调查人员还计划查明所有 精神分裂症将用于未来的连锁不平衡研究， 在当前项目中发现的潜在联系领域。 2)相对 研究人员将对最大的家系进行表型分析， 使用标准诊断表型以及两个最 精神分裂症、SPEM和P50感觉门控的有希望的内表型， 其优点是具有更高的透明度和更清晰的定义 继承模式。 3)为了对这些家系进行基因分型， 调查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 根据每项研究的以下具体计划进行分析。 为 研究1，将使用精神分裂症表型进行连锁分析 为了验证主基因的作用导致 精神分裂症 对于研究2，使用心理生理学 将使用内表型。 研究人员将使用疾病状态 和两种内表型来形成复合定量表型 这将代表精神分裂症的责任。 他们将遵循。 在研究1中发现的所有阳性结果中， 表型的定量连锁分析。