Utilizing Polygenic Risk to Understand and Improve Outcomes: A Model For Overturning Health Disparities Through Minority-Enriched Genomics Healthcare

利用多基因风险来理解和改善结果：通过少数族裔丰富的基因组医疗保健推翻健康差异的模型

• 批准号: 10852564
• 负责人: Hakon Hakonarson
• 金额: $ 71.16万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10852564
• 关键词: 18 year old; Adherence; Adult; African American population; Area; Attitude; Behavior; Body Image; Caregivers; Child; Childhood; Clinic; Clinical Decision Support Systems; Collaborations; Communication; Communities; Computerized Medical Record; Data; Disease; Disease Management; Education; Enrollment; Genetic; Genetic Risk; Genome; Genomics; Genotype; Goals; Health; Health Personnel; Health Professional; Health Promotion; Health behavior; Healthcare; Individual; Infrastructure; Intervention; Interview; Link; Marketing; Minority; Minority Groups; Minority Recruitment; Modeling; Motivation; Obesity; Outcome; Outcome Assessment; Outcome Measure; Paper; Parents; Participant; Patient Recruitments; Patients; Pediatric Hospitals; Perception; Performance; Persons; Phase; Phenotype; Philadelphia; Primary Care; Protocols documentation; Provider; Questionnaires; Reaction; Recommendation; Reporting; Research; Risk; Risk Assessment; Risk Estimate; Sampling; Site; Structure; System; Technology; Underserved Population; United States; behavior change; biobank; care outcomes; clinical decision support; clinical practice; coronavirus disease; design; dietary; disorder risk; effectiveness evaluation; empowerment; ethical, legal, and social implication; ethnic minority; experience; genetic information; genome-wide; health assessment; health disparity; high risk; improved; improved outcome; novel; patient portal; pediatric patients; polygenic risk score; primary care provider; primary outcome; programs; psychosocial; racial minority; recruit; repository; self esteem; social stigma; success; trait

ABSTRACT This program is focused on validating and implementing polygenic risk scores (PRS) to 750 participants at the Children’s Hospital of Philadelphia. Under the parent eMERGE program, CHOP established an efficient enrollment, engagement, and retention protocol that includes targeted recruitment, enhanced communication with participants and healthcare professionals, boosted analysis and EMR integration, and a dynamic education program focusing on AAs in order to achieve long-term success and improved health outcomes. The program is already returning risk reports to the EMR, exploring relevant ethical, legal, and social implications (ELSI), and investigating a range of important outcomes post-return-of-results. CHOP is on target to meet all its major milestones, with the requisite programmatic infrastructure fully operational. Building on these successes, we propose a range of sub-projects to supplement the existing scientific agenda. 1. Recruit and engage 750 additional participants (>75% minority/underserved): To date, 74% of the 847 participants recruited to CHOP are from minority/underserved populations, primarily AAs. We aim to expand the program across additional clinics, all of which would be managed under the existing infrastructure. We will return genomic risk estimates to all 750 additional participants and assess healthcare outcomes across key disease areas and collect relevant data and assess outcomes for both patients and providers. 2. Examine ethical, legal, and social implications (ELSI) of return of genomic risk estimates: Qualitative interviews will explore reactions to receiving a risk report incorporating polygenic risk scores among both parents of pediatric participants and participants over 18 years of age. Primary outcomes will be the identification of themes related to the perception of 1) self-esteem and body image; 2) stigma; and 3) behavior change, and barriers, corresponding to recommendations for the management of disease risk. 3. Assess actions and interactions between pediatric primary care providers (PCP) and parents of pediatric patients who received a high-risk GIRA: Through semi-structured interviews of PCPs, we will be empowered to assess the effectiveness of the GIRA return and CDS in supporting the provider in clinical practice including communication with parents/caregivers. This will provide a detailed analysis of the impact of EMR-based interventions on patients and providers in the pediatric context, supplementing existing Network-wide efforts to capture quantitative outcomes with novel qualitative data.

抽象的 该计划的重点是验证和实施对750名参与者的多基因风险分数（PR） 费城儿童医院。在父母出现的计划下，Chop建立了一个高效的 包括有针对性招聘，增强沟通的入学，参与度和保留协议 与参与者和医疗保健专业人员，增强分析和EMR集成以及动态 为了取得长期成功并改善健康成果的教育计划。 计划已经将风险报告退还给EMR，探索相关的道德，法律和社会影响 （ELSI），并调查一系列重要结果。切碎的目标是满足所有目标 它的主要里程碑，必要的程序基础架构完全运行。建立在这些基础上 成功，我们提出了一系列次项目，以补充现有的科学议程。 1。招募并聘请750名其他参与者（> 75％的少数民族/服务不足）：迄今为止，有74％的参与者 被招募的参与者来自少数民族/服务不足的人群，主要AA。我们旨在扩展 该计划跨越了其他诊所，所有这些计划都将在现有基础设施下进行管理。我们将 回报基因组风险估计对所有750个其他参与者和关键的评估医疗保健结果 疾病区域并为患者和提供者收集相关的数据和评估结果。 2。检查基因组风险估计回报的道德，法律和社会影响（ELSI）：定性 访谈将探索对收到风险报告的反应 小儿参与者和18岁以上的参与者的父母。主要结果将是 识别与1）自尊和身体形象相关的主题； 2）污名； 3）行为 变化和障碍，对应于管理疾病风险的建议。 3.评估小儿初级保健提供者（PCP）与小儿父母之间的行动和互动 接受高风险GIRA的患者：通过对PCP的半结构化访谈，我们将有能力 评估GIRA回报和CD在支持提供商临床实践中的有效性，包括 与父母/照顾者沟通。这将详细分析基于EMR的影响 在儿科环境下对患者和提供者的干预措施，补充现有的网络范围内的努力 用新颖的定性数据捕获定量结果。

项目成果

Rare recurrent copy number variations in metabotropic glutamate receptor interacting genes in children with neurodevelopmental disorders.

• DOI: 10.1186/s11689-023-09483-z
• 发表时间: 2023-04-29
• 期刊: Journal of neurodevelopmental disorders
• 影响因子: 4.9

Genetic architecture of type 1 diabetes with low genetic risk score informed by 41 unreported loci.

• DOI: 10.1038/s42003-021-02368-8
• 发表时间: 2021-07-23
• 期刊: Communications biology
• 影响因子: 5.9
• 作者: Qu HQ;Qu J;Bradfield J;Marchand L;Glessner J;Chang X;March M;Li J;Connolly JJ;Roizen JD;Sleiman P;Polychronakos C;Hakonarson H
• 通讯作者: Hakonarson H

Insights into non-autoimmune type 1 diabetes with 13 novel loci in low polygenic risk score patients.

• DOI: 10.1038/s41598-021-94994-9
• 发表时间: 2021-08-06
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Qu J;Qu HQ;Bradfield JP;Glessner JT;Chang X;Tian L;March M;Connolly JJ;Roizen JD;Sleiman PMA;Hakonarson H
• 通讯作者: Hakonarson H

Improved genetic risk scoring algorithm for type 1 diabetes prediction.

• DOI: 10.1111/pedi.13310
• 发表时间: 2022-05
• 期刊: Pediatric diabetes
• 影响因子: 3.4
• 作者: Qu HQ;Qu J;Glessner J;Liu Y;Mentch F;Chang X;March M;Li J;Roizen JD;Connolly JJ;Sleiman P;Hakonarson H
• 通讯作者: Hakonarson H

Attitudes among Parents towards Return of Disease-Related Polygenic Risk Scores (PRS) for Their Children.

• DOI: 10.3390/jpm12121945
• 发表时间: 2022-11-23
• 期刊: JOURNAL OF PERSONALIZED MEDICINE
• 作者: Terek, Shannon;Del Rosario, Maya C.;Hain, Heather S.;Connolly, John J.;Behr, Meckenzie A.;Harr, Margaret;Hakonarson, Hakon;Holm, Ingrid A.
• 通讯作者: Holm, Ingrid A.