Health Disparities of Patients with Fragile X from Diverse Racial & Ethnic Groups

项目摘要 脆性X综合征(FXS)是导致智力残疾和自闭症的最常见的单基因原因。 对在专科诊所就诊的患者进行的临床研究表明，这种X连锁疾病具有 对患者和家属的健康和福祉产生重大影响。FXS仍然显著 尽管越来越重视FXS患者的身份识别、患者倡导和 基因检测的可及性。这种情况在种族和民族群体中的影响尚不清楚， 共病的发生率和患病率尚未利用代表性人群进行表征。 一个尚未得到满足的需求是开发能够提醒医生潜在的新的预筛查方法 未诊断的病例，并将他们转介进行基因检测。这项申请提出的研究不仅将 与FXS相关的临床风险的高级知识，但也将提供对创新 预先筛查方法，可以改善对其他复杂的诊断不足的情况的诊断实践。 这项研究将是最大规模的人群水平的健康特征研究。 来自不同种族和民族患者群体的FXS。来自15个以上的电子健康记录(EHR) 摩羯座(芝加哥地区以患者为中心的结果研究网络)的100万名患者将被使用 为了这项研究。摩羯座包括11个不同的医疗保健系统/地点(有一家FXS专科诊所) 大都会芝加哥。已经确定了1008名患者，他们的 EHR(318名女性，690名男性)，其中293人为非白人，110人为西班牙裔，其他人为非白人 西班牙裔白人。包括来自不同种族和民族的患者，并利用以发现为导向的 方法和人工智能(AI)技术，我们提议的研究将评估表型 FXS患者的个体特征更能代表美国人口。 我们的具体目标是：(1)检测不同类型患者的FXS诊断率(和漏诊率) 种族和民族；(2)表征不同种族和民族的FXS患者的诊断模式 以及(3)建立一个人工智能辅助的预先筛查工具，以发现患有FXS的潜在病例 尚未得到诊断，并在不同种族和民族的患者群体中验证该工具。此外，我们 将通过描述年龄上的不同/相似之处来调查使用专科诊所的影响 拉什脆弱X诊所服务的患者之间的诊断、诊断奥德赛和卫生保健利用 大学和来自摩羯座其他网站的患者。我们组织了一个由多学科科学家组成的团队 拥有生物统计学、生物医学信息学、遗传学、儿科学、发展心理学、 流行病学和社会科学。具有将电子病历数据用于临床和翻译的丰富经验 研究，以及长期成功地进行关于FXS的多机构合作研究， 我们的团队有非凡的能力来实现这些研究目标。

Project Summary Fragile X syndrome (FXS) is the most prevalent monogenic cause of intellectual disability and autism. Clinical studies on patients being seen in specialized clinics have shown that this X-linked disorder has a substantial impact on the health and well-being of patients and families. FXS remains significantly underdiagnosed despite increased emphasis on identification of individuals with FXS, patient advocacy, and accessibility of genetic testing. The impact of this condition across racial and ethnic groups is unknown and the rate and prevalence of co-occurring conditions has not yet been characterized using representative populations. An unmet need exists to develop novel pre-screening approaches that are able to alert physicians to potentially undiagnosed cases and refer them for genetic testing. This application proposes research that will not only advance knowledge of clinical risk associated with FXS but will also offer insight into development of innovative pre-screening approaches that can improve diagnostic practices for other complex underdiagnosed conditions. The present research will be the largest population-level study of health characteristics of individuals with FXS from diverse racial and ethnic patient groups. The electronic health records (EHRs) from more than 15 million patients in CAPriCORN (the Chicago Area Patient-Centered Outcomes Research Network) will be used for this study. CAPriCORN includes 11 different health care systems/sites (with one FXS Specialized Clinic) in metropolitan Chicago. 1008 patients have been identified who have a diagnostic code for FXS in their EHRs (318 females, 690 males) of whom 293 are Non-White, 110 are Hispanic, and the others are non- Hispanic Whites. By including patients from diverse racial and ethnic groups, and by utilizing discovery-oriented approaches and artificial intelligence (AI) techniques, our proposed research will evaluate phenotypic characteristics of individuals with FXS more representative of the US population. Our Specific Aims are: (1) To detect the rate of FXS diagnosis (and under-diagnosis) in patients from diverse racial and ethnic groups; (2) To characterize the diagnostic patterns in FXS patients from diverse racial and ethnic groups; and (3) To construct an AI-assisted pre-screening tool to find potential cases with FXS who have not yet been diagnosed and validate the tool with racially and ethnically diverse patient groups. Additionally, we will investigate the impact of access to specialty clinics by characterizing the differences/similarities in age of diagnosis, diagnostic odyssey, and health care utilization between patients served by the Fragile X Clinic at Rush University and patients from other CAPriCORN sites. We have organized a multidisciplinary team of scientists with expertise in biostatistics, biomedical informatics, genetics, pediatrics, developmental psychology, epidemiology, and social science. With substantial experience in using EHR data for clinical and translational research, and with a long successful track record of conducting collaborative multi-institutional studies on FXS, our team has exceptional ability to achieve these research goals.