GENETIC ANALYSIS OF PSYCHOSIS

描述(根据申请者的摘要改编)：我们将研究一个相对 基因同质群体来检验基因的假说 这些因素与精神分裂症有关。这项研究将集中在两个方面 人口。第一个来自亚速尔群岛，这是一个由9个岛屿组成的群岛 大西洋，是葡萄牙的一个国家。亚速尔群岛有一个集中的 卫生系统。岛屿上的所有十名精神病医生都在与 我们在这个项目上。第二个人口来自葡萄牙大陆。 大多数阿佐里亚人的种群都来自这个种群基数。 有多个受影响成员患有精神分裂症的家庭将被研究 同时采用参数和非参数分析策略。我们 预计大约有100个家庭被隔离为精神分裂症， 包括300多名受影响的家庭成员。一个互补的战略将 用于研究候选基因座。我们将对225名受试者进行抽样研究 精神分裂症患者及其父母(总计n=675人) 单倍型相对风险和传递/不平衡检验策略。 这一策略确保了我们对每个受试者的所有祖先的控制， 使用来自两个亲本的非遗传单倍型。第三 样本将包括所有其他Azorean精神分裂症患者，他们 同意有希望地参与，实现近距离完成 亚速尔群岛精神分裂症患者的确诊。这将是一个 考虑到连锁不平衡方法的性质，有价值的样本 并为我们提供了一个独特的流行病学框架。 这些互补的策略将使我们能够交叉验证任何积极的 结果。对表型的仔细诊断定义将基于 使用诊断性访谈的详细结构化临床数据 遗传研究(DIGS)，我们已经翻译成葡萄牙语。我们的 该项目旨在捕获非常完整的患者病史 疾病，以及能够前瞻性地跟踪大多数受试者 很长一段时间。这将是非常有价值的实现 诊断确定性，并将假阳性降至最低。一个重要的新消息 除了这项提议，怀特黑德/麻省理工学院基因组研究中心， 它将执行全基因组扫描并协作进行所有数据分析 为了这个项目。

DESCRIPTION (Adapted from applicant's abstract): We will study a relatively genetically homogeneous population to test the hypotheses that genetic factors are linked to schizophrenia. The study will focus on two populations. The first is from the Azores, a nine island archipelago in the Atlantic ocean that is a Portuguese state. The Azores have a centralized health system. All ten psychiatrists on the islands are collaborating with us on this project. The second population is from continental Portugal. The majority of the Azorean population is derived from this population base. Families with multiple affected members with schizophrenia, will be studied employing both parametric and non-parametric analytic strategies. We projected approximately 100 families segregating for schizophrenia, including over 300 affected family members. A complementary strategy will be used to study candidate loci. We will study a sample of 225 subjects suffering from schizophrenia and their parents (Total n=675) employing the haplotype relative risk and the transmission/disequilibrium test strategies. This strategy insures that we control for all ancestry for each subject, using the uninherited haplotype derived from the two parents. The third sample will include all other Azorean patients with schizophrenia, who agreed to participate in hopefully, achieving close to complete ascertainment of patients with schizophrenia in the Azores. This will be a valuable sample for linkage disequilibrium approaches given the nature of the Azorean population and provide us with a unique epidemiologic frame. These complementary strategies will allow us to cross validate any positive results. The careful diagnostic definition of phenotype will be based on detailed structured clinical data employing the Diagnostic Interview for Genetic Studies (DIGS), which we have translated into Portuguese. Our project is designed to capture a very complete history of the patients illness, as well as to be able to follow most subjects prospectively for a long period of time. This will be extremely valuable for achieving diagnostic certainty and minimizing false positives. An important new addition to this proposal is the Whitehead/MIT Center for Genome Research, that will perform a genome-wide scan and collaborate on all data analysis for the project.