Abnormal Eye Movement in Schizophrenia: Genome-Wide Scan

描述：（申请人提供）： 这是R01提案的第三次提交。这项提议的目的是进行全基因组扫描，寻找与精神分裂症相关的内在表型的联系，即在平稳追踪眼球运动（SPEM）任务期间领导扫视的频率升高。SPEM异常与精神分裂症相关近100年，并被认为是精神分裂症遗传风险的潜在标志物超过20年。在过去的几年里，我们一直专注于确定SPEM的组成部分（S）最具体的精神分裂症和最敏感的假定遗传风险。在SPEM任务中，领导扫视的频率升高似乎是SPEM功能的敏感和特定的组成部分。领先扫视的频率升高在精神分裂症患者中比一般人群或注意缺陷/多动障碍、自闭症或双相情感障碍患者更常见;在精神分裂症患者的亲属中更常见;似乎与精神分裂症的假定遗传风险有关;并且在6 - 80岁之间可用。此外，升高的主导扫视频率在一般人群中呈三态分布，在正常人群和受影响人群中具有相似的方差，并且在精神分裂症家族中以与主基因效应一致的方式分离。这些结果表明，这种表型是适合连锁分析。为了增加样品的均一性和遗传负荷，将使用两种方法。首先（目标1），将从多个受累家族（2个或更多精神分裂症家族成员）中收集扩展谱系。第二（目标#2），通过利用精神分裂症先证者发病年龄非常早（12岁或更小）的家庭来寻求增加的遗传负荷。将使用能够检测数量性状的遗传效应的方法来评估两组中的连锁。

DESCRIPTION: (provided by applicant): This is the third submission of this R01 proposal. The aims of this proposal are to perform a genomewide scan looking for linkage to a schizophrenia-associated endophenotype, an elevated frequency of leading saccades during a smooth pursuit eye movement (SPEM) task. SPEM abnormalities have been associated with schizophrenia for almost 100 years, and have been suggested as a potential marker of genetic risk for schizophrenia for over 20 years. Over the last several years, we have focused on identifying the component(s) of SPEM most specific to schizophrenia and most sensitive to presumed genetic risk. An elevated frequency of leading saccades during a SPEM task appears to be a sensitive and specific component of SPEM function. Elevated frequency of leading saccades is more common in individuals with schizophrenia than in the general population or in individuals with attention deficit/hyperactivity disorder, autism, or bipolar disorder; is more common in relatives of individuals with schizophrenia; appears to sort with presumed genetic risk for schizophrenia; and is usable from 6-80 years of age. Additionally, elevated leading saccade frequency is tri-modally distributed in the general population, has a similar variance in normal and affected populations, and segregates in families with schizophrenia in a manner consistent with a major gene effect. These findings suggest that this phenotypc is appropriate for linkage analysis. To increase the homogeneity and genetic loading of the sample, two approaches will be used. First (aim #1), extended pedigrees will be gathered from multi-affected families (2 or more family members with schizophrenia). Second (aim #2), increased genetic loading will be sought by utilizing families in which the schizophrenic probands have very early ages of onset, at age 12 years or younger. Linkage in both groups will assessed using methods capable of detecting genetic effects on quantitative traits.