Genetic architecture of transdiagnostic psychosis symptom dimensions

跨诊断精神病症状维度的遗传结构

• 批准号: 10572178
• 负责人: Dana Lapato
• 金额: $ 15.83万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-15 至 2026-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10572178
• 关键词: Address; Affective; African; Age of Onset; Award; Basic Science; Behavior; Behavioral; Biological; Biological Markers; Bipolar Disorder; Bipolar I; Clinical; Complement; Country; Data; Delusions; Dementia; Diagnosis; Diagnostic; Diagnostic and Statistical Manual of Mental Disorders; Dimensions; Disease; European ancestry; Factor Analysis; Foundations; Funding; Genetic; Genetic Predisposition to Disease; Genetic Research; Genetic Variation; Genetic study; Genomics; Goals; Hallucinations; Heritability; Individual; Interview; Investigation; K-Series Research Career Programs; Latinx; Lead; Major Depressive Disorder; Manic; Measures; Medical; Mental Depression; Mental disorders; Mentors; Mentorship; Meta-Analysis; Methodological Studies; Methods; Modernization; Molecular Genetics; Mood Disorders; National Institute of Mental Health; Nature; Neurocognitive; Neurologic; Outcome; Participant; Patients; Personal Satisfaction; Phenotype; Population Heterogeneity; Psychiatry; Psychometrics; Psychoses; Psychotic Disorders; Publishing; Questionnaires; Research; Research Personnel; Risk; Schizoaffective Disorders; Schizophrenia; Secure; Signs and Symptoms; Structure; Symptoms; Testing; Training; Translational Research; Twin Multiple Birth; Work; biobank; career; career development; case control; clinically relevant; cohort; comorbidity; demographics; design; disease classification; experience; family genetics; genetic architecture; genome wide association study; genomic data; improved; insight; motor behavior; polygenic risk score; psychiatric genomics; psychogenetics; psychotic; psychotic symptoms; research study; sex; skills; social health determinants; statistics; substance use; training opportunity

Project Summary This K Award will provide formalized training, mentorship, and research experience in psychiatric nosology, advanced psychometrics, and multi-ancestry statistical genetics methods requisite for the candidate to achieve her long-term career goal of becoming an independent investigator capable of leading high-impact studies, securing external funding, and staying apace with the rapidly evolving nature of modern psychiatric genomics research. Successful completion of this project will refine our understanding of the genetic architecture of psychosis and enable Dr. Lapato to integrate dimensional phenotypic approaches with molecular genetics so that she can lead large-scale analyses required for robust results in genetically diverse cohorts. The overarching research goal of this proposal is to investigate the genetic architecture of psychosis as it presents in schizophrenia, schizoaffective disorder, and bipolar I disorder. The data come from the Genomic Psychiatry Cohort. Psychosis signs and symptoms were assessed by trained clinical staff using a semi-structured clinical interview. Under the guidance of her K01 mentorship team led by Dr. Kenneth Kendler, Dr. Lapato will use exploratory and confirmatory factor analysis to derive empirical measures of psychosis symptom dimensions. She will conduct genome-wide association (GWA) testing and derive post-GWA metrics (e.g., SNP heritability, polygenic risk scores) using both single and multi-ancestry methods. Key demographic, clinical, behavioral, and environmental variables (including social determinants of health) will be used to validate the psychosis symptom factors and their polygenic risk scores. Successful completion of this project will refine our understanding of the genetic architecture of psychosis and equip Dr. Lapato with the requisite skills to progress on to a successful career in psychiatric genetics research.

项目概要 该 K 奖将提供精神病学方面的正式培训、指导和研究经验 疾病分类学、高级心理测量学和多祖先统计遗传学方法是 候选人实现成为独立调查员的长期职业目标 能够领导高影响力的研究、获得外部资金并与时俱进 现代精神病学基因组学研究的快速发展本质。顺利完成本次 该项目将加深我们对精神病遗传结构的理解，并使博士能够。 拉帕托将维度表型方法与分子遗传学相结合，以便她能够 领导在遗传多样性队列中获得稳健结果所需的大规模分析。这 该提案的总体研究目标是调查精神病的遗传结构 正如它在精神分裂症、分裂情感性障碍和 I 型双相情感障碍中所表现的那样。数据来了 来自基因组精神病学队列。精神病体征和症状由经过培训的人员进行评估 临床工作人员使用半结构化临床访谈。在她的K01导师的指导下 由 Kenneth Kendler 博士和 Lapato 博士领导的团队将使用探索性和验证性因素分析 得出精神病症状维度的经验测量。她将进行全基因组研究 关联 (GWA) 测试并得出 GWA 后指标（例如，SNP 遗传力、多基因风险 分数）使用单祖先和多祖先方法。关键人口统计、临床、行为和 环境变量（包括健康的社会决定因素）将用于验证 精神病症状因素及其多基因风险评分。本项目顺利完成 将加深我们对精神病遗传结构的理解，并为拉帕托博士提供 在精神遗传学研究领域取得成功职业生涯所需的技能。