Leveraging human genetics to overcome complex diagnostic challenges, evaluation of pan-ancestry polygenic scores to reduce misdiagnosis of narcolepsy and circadian rhythm sleep wake disorders.

利用人类遗传学克服复杂的诊断挑战，评估泛祖多基因评分以减少发作性睡病和昼夜节律睡眠觉醒障碍的误诊。

• 批准号: 10576448
• 负责人: Jacqueline Marie Lane
• 金额: $ 71.61万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-16 至 2028-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10576448
• 关键词: Acceleration; Address; Autoimmune; Awareness; Catalogs; Circadian Rhythms; Clinic; Clinical; Complex; Computer software; Databases; Diagnosis; Diagnostic; Diagnostic tests; Disease; Early Diagnosis; Early identification; European ancestry; Evaluation; Face; Genes; Genetic; Genetic Risk; Goals; Healthcare; Healthcare Systems; Hospitals; Human Genetics; Individual; Inequality; Insurance Coverage; Medicine; Mental Depression; Narcolepsy; Pathogenicity; Patients; Pharmaceutical Preparations; Phase; Phenotype; Population; Primary Care Physician; Process; Rare Diseases; Records; Risk; Risk Factors; Risk Marker; Sleep; Sleep Disorders; Sleeplessness; Testing; Unnecessary Procedures; Variant; Visit; Woman; Work; accurate diagnosis; biobank; circadian; cohort; disorder risk; early screening; exome; exome sequencing; genetic predictors; genetic variant; genome sequencing; genome wide association study; health disparity; health inequalities; improved; large-scale database; medical specialties; novel; people of color; personalized predictions; polygenic risk score; rare variant; repository; risk prediction; risk variant; routine screening; screening; sleep behavior; timeline; trait

Project Summary/Abstract One of the biggest challenges in rare disease is accuracy and timeliness of patient diagnosis. On average it takes 6 years for an accurate diagnosis, delaying treatment and creating substantial burden at the levels of individual, familial and healthcare systems with an estimated $750 billion spent on unnecessary procedures. Misdiagnosis also widens inequalities further, as misdiagnosis is more common among women and people of color. Therefore, there is an urgent need to improve diagnosis. Genetic risk predictions can improve diagnosis, with particular clinical utility in the specific setting where large barriers to diagnosis exist, such as rare sleep disorders. The rare sleep disorders narcolepsy and circadian rhythm sleep wake disorders face large hurdles to diagnosis, where 20% of primary care physicians are unaware that sleep medicine exists as a specialty, routine screening for sleep disorders is nearly absent, diagnostic tests require overnight visits to a limited number of specialized clinics, and insurance coverage for common diagnostic tests is non-existent. In contrast to the current diagnostic landscape for sleep disorders, genetic risk prediction is relatively inexpensive and easily accessible. In order to integrate genetic risk into the diagnosis and treatment pipeline, we must first have genetic predictors of risk applicable across multiple ancestry groups, or we risk widening inequities in healthcare further. To address the challenge of timely patient diagnosis in sleep disorders, we propose to leverage large exome sequence repositories to generate rare variant risk scores, expand the current known common polygenic scores to multiple genetic ancestries, and ultimately test the ability of both the rare and common polygenic scores to predict risk of rare sleep and circadian disorders in a large-scale hospital database with the goal to integrate flags in patient records.

项目总结/文摘