Genetic architecture of transdiagnostic psychosis symptom dimensions

跨诊断精神病症状维度的遗传结构

基本信息

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
项目类别：
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

项目摘要

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.

项目摘要该K奖将提供精神病的正式培训，指导和研究经验必要候选人实现她成为独立调查员的长期职业目标能够领导高影响研究，获得外部资金并与现代精神病基因组学研究的快速发展的本质。成功完成项目将完善我们对精神病遗传结构的理解，并使博士 lapato将尺寸表型方法与分子遗传学相结合，以便她可以在遗传多样的队列中所需的良好结果所需的大规模分析。这该建议的总体研究目标是研究精神病的遗传结构由于它在精神分裂症，精神分裂症和双相情感障碍中表现出来。数据来了来自基因组精神病学队列。精神病的体征和症状是通过训练的临床人员使用半结构化临床访谈。在她的K01指导的指导下 Lapato博士由Kenneth Kendler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度量。她将进行全基因组协会（GWA）测试并得出GWA后指标（例如SNP遗传力，多基因风险分数）使用单一和多符合方法。关键人口，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。成功完成该项目将完善我们对精神病遗传结构的理解，并为Lapato博士配备在精神遗传学研究领域成功职业生涯的必要技能。