Statistical methods to localize disease heritability and identify biological mechanisms

定位疾病遗传性并确定生物学机制的统计方法

• 批准号: 10379539
• 负责人: Benjamin Michael Neale
• 金额: $ 12.54万
• 依托单位: BROAD INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10379539
• 关键词: Address; Administrative Supplement; Affect; African American; Attention; Biological; Bipolar Disorder; Chronic; Clinical; Complex; Consensus; Data; Development; Disease; European; Evaluation; General Population; Genetic; Genetic Risk; Genetic Variation; Genome; Heritability; Individual; Localized Disease; Measures; Medicine; Mental disorders; Methodology; Performance; Phenotype; Population; Population Heterogeneity; Process; Psychoses; Research; Risk; Risk Assessment; Sampling; Schizophrenia; Statistical Methods; Supervision; Training; Variant; Work; base; experience; genetic analysis; genetic association; genetic variant; genome wide association study; high risk; improved; meetings; parent grant; polygenic risk score; preventive intervention; success; symptomatology; tool; trait; virtual; working group

PROJECT SUMMARY/ABSTRACT Schizophrenia is a psychotic, chronic and disabling disorder, affecting about 1% of the general population. Identifying individuals at risk for developing this disorder is crucial for establishing preventive interventions. So far, the assessment of risk of developing psychosis has been based primarily on clinical features, the accuracy of which is not optimal for development and implementation of preventive interventions. Evaluation of psychosis risk improves when genetic risk is taken into account. Thus, development of robust measure of genetic risk for psychosis offers a possibility of improvement in assessment of psychosis risk. Recent success of genome- wide association studies in schizophrenia allows the calculation of a polygenic risk score that reflects a cumulative impact of common genetic variants on the development of the disorder and related phenotypes. The aim of this study is to examine the performance of such schizophrenia polygenic score on evaluation of psychosis risk in a sample of individuals at high risk of developing psychosis based on clinical features. The examination will extend to the performance of the genetic score in individuals of non-European descent. This will advance our tools for identification of psychosis risk and, consequently, its preventive interventions in diverse populations.

项目总结/摘要 精神分裂症是一种精神病，慢性和致残性疾病，影响约1%的一般 人口识别有发展这种疾病风险的个体对于建立 预防性干预。到目前为止，对精神病风险的评估一直是基于 主要是临床特征，其准确性对于开发来说不是最佳的， 实施预防性干预措施。当遗传性疾病发生时，精神病风险评估得到改善 风险被考虑在内。因此，发展精神病遗传风险的稳健措施 为精神病风险评估提供了改进的可能性。最近基因组的成功- 精神分裂症的广泛关联研究允许计算多基因风险评分， 反映了常见遗传变异对疾病发展的累积影响， 相关表型本研究的目的是检查这种精神分裂症的表现 多基因评分在精神病风险评估中的应用 基于临床特征的精神病。考试范围将扩大到 非欧洲血统个体的遗传评分。这将推进我们的识别工具 精神病的风险，因此，它的预防干预措施在不同的人群。