PLEIOTROPIC EFFECTS OF GENES LINKED TO SCHIZOPHRENIA

与精神分裂症相关的基因的多效性

• 批准号: 7174618
• 负责人: DEBORAH L LEVY
• 金额: $ 57.47万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-01 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7174618
• 关键词: Accounting; Affect; Biological; Candidate Disease Gene; Clinical; Cognitive; Collection; Compatible; Complex; Data; Disease; Dominant Genes; Dysmorphology; Eye; Family; First Degree Relative; Functional disorder; Gene Family; General Population; Genes; Genetic; Genetic Markers; Goals; Individual; Investments; Laboratories; Light; Link; Lod Score; Measures; Methods; Modeling; Molecular Genetics; National Institute of Mental Health; Neurobiology; Nuclear; Numbers; Pathology; Pathway interactions; Phenocopy; Phenotype; Physiological; Positioning Attribute; Predisposition; Probability; Process; Range; Recurrence; Relative (related person); Reporting; Risk; Risk Factors; Sampling; Schizophrenia; Semantics; Siblings; Smooth Pursuit; Spottings; Symptoms; System; Thinking; Work; cost; craniofacial; density; design; disease phenotype; endophenotype; genetic linkage; interest; oculomotor; proband; success; trait; transmission process

DESCRIPTION (provided by applicant): For many years this laboratory has focused intensively on characterizing schizophrenia-related traits (SRTs) as qualitative and quantitative phenotypes for schizophrenia. Three of these SRTs - thought disorder with schizophrenic features, eye tracking dysfunction and a craniofacial anomaly involving the frontonasal-maxilllary junction - stand out as especially probative for clarifying the neurobiological interpretation of schizophrenia susceptibility loci. Each of these traits has a much higher recurrence in relatives of schizophrenics than in schizophrenics. Moreover, unlike schizophrenia, which is generally thought to involve a number of co-acting genes, the family data on the SRTs are consistent with monogenic transmission models, and may therefore clarify the complex genetics of schizophrenia. The massive investment by NIMH in searching for genes for schizophrenia has resulted in an impressive number of promising candidate genes and chromosomal regions. Our progress in characterizing SRTs places us in an ideal position to determine whether any of these SRTs is linked to identified genes and "warm spot" regions for schizophrenia. We recognize, of course, that not all of the reported linkages will be replicable, but the probability is high that some of them are authentic, and the added cost of taking an inclusive view of the candidate loci is modest. Our power analyses show that the density of individuals affected with the SRTs in families of a schizophrenic proband is sufficiently high that, given a candidate locus associated with the SRT, the probability of our being able to detect that relationship is very high. If any of the genetic loci that have been linked to schizophrenia can be shown to be linked to any of the SRTs, it would open the way for building a neurobiological bridge between the disease phenotype and its genetic underpinnings, and it would add considerably to the confidence one can have in the reported linkages. Because of our laboratory's long involvement in investigating schizophrenia-related traits, the substantial number of families already acquired and thoroughly studied with respect to these traits and the expertise of our statistical and molecular genetics collaborators, our laboratory is uniquely positioned to carry out these studies.

描述（由申请人提供）：多年来，该实验室一直集中在将精神分裂症相关性状（SRT）表征为精神分裂症的定性和定量表型。这些SRT中的三个 - 具有精神分裂症特征的思想障碍，眼睛跟踪功能障碍以及涉及额骨 - 大小交界的颅面异常 - 特别有证明是阐明对精神分裂症易感性位点的神经生物学解释。这些特征中的每一个在精神分裂症患者的亲属中的复发性都比精神分裂症患者高得多。此外，与普遍认为涉及许多共同作用基因的精神分裂症不同，SRT上的家庭数据与单基因传递模型一致，因此可以阐明精神分裂症的复杂遗传学。 NIMH在寻找精神分裂症基因的大量投资导致了令人印象深刻的有前途的候选基因和染色体区域。我们在表征SRTS方面的进展使我们处于理想的位置，以确定这些SRT是否与精神分裂症的已识别基因和“温暖的斑点”区域相关。当然，我们认识到，并非所有报告的链接都可以复制，但是其中一些是真实的概率，并且对候选基因座的包容性看法的增加成本很小。我们的功率分析表明，精神分裂症患者家族中受SRT影响的个体的密度足够高，鉴于与SRT相关的候选基因座，我们能够检测到这种关系的可能性很高。如果可以证明与精神分裂症相关的任何遗传基因座都与任何SRT相关联，它将为在疾病表型及其遗传基础之间建立神经生物学桥梁开辟道路，并且它将在报告的联系中具有相当大的信心。由于我们的实验室长期参与了与精神分裂症相关的特征的参与，因此已经在这些特征方面已经获得和彻底研究了大量家庭，以及我们的统计和分子遗传学合作者的专业知识，我们的实验室是独特的，可以进行这些研究。