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.

摘要 该计划的重点是验证和实施多基因风险评分（PRS），以750名参与者在 费城儿童医院在母公司eMERGE计划下，CHOP建立了一个有效的 招募、参与和保留协议，包括有针对性的招募、加强沟通 与参与者和医疗保健专业人员一起，促进了分析和EMR集成， 教育计划侧重于AA，以实现长期的成功和改善的健康结果。的 一个项目已经在向EMR反馈风险报告，探索相关的伦理、法律的和社会影响 （ELSI），并在结果返回后调查一系列重要结果。CHOP的目标是满足所有 其主要里程碑，必要的方案基础设施全面运作。根据这些 成功后，我们提出了一系列子项目来补充现有的科学议程。 1.招募和参与750名额外参与者（> 75%为少数族裔/服务不足）：迄今为止，847名参与者中的74% CHOP招募的参与者来自少数/服务不足的人群，主要是AA。我们的目标是扩大 该计划将在更多的诊所实施，所有这些诊所都将在现有的基础设施下管理。我们将 向所有750名额外参与者返回基因组风险估计值，并评估关键 收集相关数据并评估患者和提供者的结果。 2.研究基因组风险评估回报的伦理、法律的和社会影响（ELSI）：定性 访谈将探讨对接受风险报告的反应，该报告将多基因风险评分纳入两个 儿童参与者的父母和18岁以上的参与者。主要成果将是 识别与以下感知相关的主题：1）自尊和身体形象; 2）耻辱; 3）行为 变化和障碍，对应于疾病风险管理的建议。 3.评估儿科初级保健提供者（PCP）和儿科家长之间的行动和互动 接受高风险GIRA的患者：通过对PCP的半结构化访谈，我们将有权 评估GIRA回报和CDS在临床实践中支持提供者的有效性，包括 与父母/照顾者沟通。这将详细分析基于电子病历的 在儿科背景下对患者和提供者进行干预，补充现有的网络范围内的努力， 用新的定性数据捕捉定量结果。

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

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.

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