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

项目摘要 脆性X综合征（FXS）是智力残疾和自闭症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染色体连锁疾病具有 对患者和家属的健康和福祉产生重大影响。FXS仍显着 尽管越来越重视FXS患者的识别，患者的宣传， 基因检测的可及性。这种情况对种族和族裔群体的影响尚不清楚， 尚未使用代表性人群对共病率和患病率进行表征。 开发新的预筛选方法的需求尚未得到满足，这些方法能够提醒医生注意潜在的 未确诊的病例，并将其转介进行基因检测。该应用程序提出的研究，不仅将 与FXS相关的临床风险的先进知识，但也将提供创新的发展洞察力， 预筛选方法，可以改善其他复杂的诊断不足的条件的诊断实践。 目前的研究将是最大的人群水平的健康特征的个人研究， 来自不同种族和民族患者群体的FXS。电子健康记录（EHR）超过15 将使用CAPriCORN（芝加哥地区以患者为中心的结局研究网络）的100万名患者 for this study研究. CAPriCORN包括11个不同的医疗保健系统/站点（有一个FXS专业诊所）， 大都市芝加哥。已经确定了1008名患者，他们的诊断代码为FXS， EHR（318名女性，690名男性），其中293名为非白人，110名为西班牙裔，其他为非白人。 西班牙白人通过纳入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，我们提出的研究将评估表型 FXS患者的特征更能代表美国人群。 我们的具体目的是：（1）检测FXS诊断率（和诊断不足）在不同的患者， （2）描述不同种族和民族的FXS患者的诊断模式， （3）建立一个人工智能辅助的预筛查工具，以发现潜在的FXS病例， 还没有被诊断出来，并与不同种族和民族的患者群体验证该工具。另外我们 将通过描述年龄的差异/相似性来调查进入专科诊所的影响， 拉什脆性X染色体诊所服务的患者之间的诊断、诊断历程和医疗保健利用 大学和其他CAPriCORN研究中心的患者。我们组织了一个多学科的科学家团队 具有生物统计学、生物医学信息学、遗传学、儿科学、发展心理学等方面的专业知识， 流行病学和社会科学。在使用EHR数据进行临床和翻译方面具有丰富的经验 研究，并具有长期成功的多机构合作研究FXS的记录， 我们的团队具有实现这些研究目标的卓越能力。

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.