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Improving the Precision of Genetic Markers for Psychotic Disorders

提高精神障碍遗传标记的精确度

基本信息

批准号：
10358535
负责人：
Katherine G Jonas
金额：
$ 20.62万
依托单位：
STATE UNIVERSITY NEW YORK STONY BROOK
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-03-05 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10358535
关键词：
Accounting Affect Anhedonia Attenuated Basic Science Biological Biological Markers Bipolar Disorder Clinical Communication County Data Delusions Development Diagnosis Diagnostic Dimensions Disease Environment Etiology Evaluation Exercise Feeling suicidal Funding Future Gene Expression Profile Genetic Genetic Markers Genetic Predisposition to Disease Genetic Risk Genetic Structures Genomics Hallucinations Health Heritability Impairment Individual Intervention Investigation Knowledge Longitudinal cohort Longitudinal cohort study Longterm Follow-up Manic Mental Health Mental disorders Methods Modeling Moods National Institute of Mental Health Other Genetics Outcome Participant Pathway interactions Patients Persons Pharmaceutical Preparations Phenotype Prognosis Prognostic Marker Psychiatry Psychopathology Psychoses Psychotic Disorders Research Research Domain Criteria Research Personnel Research Training Resources Risk Risk Behaviors Running Sampling Schizophrenia Scoring Method Severity of illness Signal Transduction Sleep Source Specificity Statistical Methods Sum Symptoms Technology Testing Training Training Programs Translational Research Treatment outcome United States United States National Institutes of Health Variant Weight biomarker validation burden of illness career clinical application clinical candidate clinical care clinically significant cohort depressive symptoms disorder risk ethnic diversity first episode psychosis follow-up functional outcomes genetic variant improved novel pleiotropism polygenic risk score psychosis risk psychosocial responsible research conduct severe mental illness simulation symptomatology tool treatment response

项目摘要

PROJECT SUMMARY Psychotic disorders account for more than 10% of mental-health-related disease burden in the United States, but it remains difficult to predict who will develop a psychotic disorder, how their illness will progress, and how they will respond to available treatments. Recent findings suggest promise for genetic markers for psychotic illnesses, but these tools are imprecise, limiting their utility for basic research and clinical application. This K08 application outlines a research and training program that will support the applicant's development towards an NIH-funded, independent research career investigating the genetic liabilities for serious mental illness. The activities outlined in this application build on the candidate's clinical and quantitative background, and through training exercises set in a resource-rich environment, facilitate the development of expertise in 1) scientific communication and responsible conduct of research; 2) statistical genetics, 3) genetics of psychotic disorders, and 4) translational research for evaluating genetic markers for clinical applications. The aim of the research outlined in this proposal is to validate a novel method of identifying polygenic risk for psychotic disorders that takes account of overlapping symptoms and common genetic vulnerabilities. This approach aims to improve the precision of polygenic risk scores. This method will be applied in an ethnically diverse sample of 30,000 individuals with psychotic disorders, identifying polygenic risk scores for both general and specific facets of psychotic symptomatology. The resulting risk scores will be validated in pooled analysis of nine longitudinal cohort studies, comprising 1,785 cases. Risk scores will be tested as predictors of psychosis onset, diagnosis, symptom trajectory, psychosocial outcomes, and treatment response. If the proposed research succeeds in identifying genetic correlates of specific dimensions of psychotic disorders that predict these important health outcomes, it will have important implications for etiological research, as it may help to identify targets for intervention. The findings would also have significance for clinical translational research, as genetic markers have potential application as aids in diagnosis and prognosis.

项目总结