The Long Life Family Study

长寿家庭研究

• 批准号: 10366972
• 负责人: Michael A. Province
• 金额: $ 15.47万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-15 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10366972
• 关键词: Address; Agreement; Area; Attitude; Bioethical Issues; Bioethics; CLIA certified; CYP2C19 gene; CYP2C9 gene; Clinical; Cohort Studies; Comprehension; Consensus; Consent; Consent Forms; Consult; Consultations; Data; Decision Making; Development; Dose; Ethical Issues; Ethics; FDA approved; Family; Family Study; Family member; Future; Genes; Genetic; Genetic Variation; Guidelines; Health behavior; Individual; Informed Consent; Infrastructure; International; Label; Laboratories; Life; Medical; Monitor; Observational Study; Participant; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Pharmacists; Pharmacogenetics; Pharmacogenomics; Phenotype; Physicians; Pilot Projects; Population Study; Positioning Attribute; Procedures; Process; Proteomics; Recommendation; Recording of previous events; Reporting; Research; Research Personnel; Role; Services; Societies; Structure; Surveys; Telephone; Testing; Time; Universities; Variant; Visit; Work; acceptability and feasibility; actionable mutation; adverse drug reaction; base; behavioral outcome; bisulfite sequencing; clinically actionable; cohort; experience; genetic variant; genome sciences; genome sequencing; indexing; metabolomics; preference; process optimization; research study; response; satisfaction; transcriptomics; whole genome; willingness

Abstract The Long Life Family Study (LLFS) is a family-based cohort of unusually healthy individuals that has whole genome sequencing (WGS) data on a majority of its participants and is currently generating large scale -omics data on its participants that includes transcriptomics, whole genome bisulfite sequencing, metabolomics and proteomics. Though LLFS does not return any incidental genetic results to study participants currently, LLFS has modified it’s consent form to ask participants whether they would like to receive incidental genetic findings in the future. The availability of WGS data in almost 4000 LLFS participants along with informed consent for return of medically actionable incidental genetic results, ideally positions LLFS to address bioethical issues related to return of genetic results in family-based cohorts. Pharmacogenetics (PGx), the study of the role of genetic variation in drug response phenotypes, is an area within genomic science that can positively impact patient management and consensus guidelines regarding specific genes and variants to be tested are now available. Thus, return of targeted PGx results that are clinically impactful and are supported by several national and international societies represent an opportunity that can be used to develop the bioethical framework for return of incidental genetic results in LLFS. We propose a pilot study at a single US field center (University of Pittsburgh) to demonstrate the feasibility and acceptability of returning limited PGx results from three genes to 200 LLFS participants. We propose to identify ten medically actionable PGx variants in three genes (CYP2C9, CYP2C19 and VKORC1) from WGS data already available in LLFS. We will confirm the observed variants in a CLIA certified laboratory, create a report summarizing the variants identified and the medications impacted by these variants and establish a study specific PGx consultation service to discuss study results with LLFS participants as needed. We propose to ascertain participant-assessed comprehension, decision making, and satisfaction with return of PGx results (Aim 1) at two time-points, immediately and three months after returning PGx results. In addition, we will leverage the family-based structure of the LLFS cohort to evaluate whether the index participants share their PGx results with their family members and ascertain the comprehension, decision making and satisfaction among family members with return of PGx results to the index study participant using a single telephone survey conducted 3 months after returning PGx results (Aim 2). Finally, we will also assess a pharmacist/physician determined impact of the PGx results on medications the LLFS participants to identify any gaps between pharmacist-assessed and participant-assessed impact of PGx results (Aim 2). At the end of this project, we will have addressed important ethical issues surrounding the return of incidental PGx results to research participants and generated pilot data to support the broader implementation of return of medically actionable incidental genetic findings to research participants.

抽象的 长寿家庭研究 (LLFS) 是一个以家庭为基础的队列，由异常健康的个体组成， 大多数参与者的基因组测序（WGS）数据，目前正在生成大规模组学 参与者的数据，包括转录组学、全基因组亚硫酸氢盐测序、代谢组学和 蛋白质组学。尽管 LLFS 目前不会向研究参与者返回任何偶然的遗传结果，但 LLFS 修改了同意书，询问参与者是否愿意接受偶然的基因发现 将来。近 4000 名 LLFS 参与者的 WGS 数据的可用性以及知情同意书 返回医学上可行的偶然遗传结果，理想地使 LLFS 能够解决生物伦理问题 与基于家庭的队列中遗传结果的返回有关。药物遗传学 (PGx)，研究药物的作用 药物反应表型的遗传变异是基因组科学中的一个领域，可以对药物反应表型产生积极影响 关于待测试的特定基因和变异的患者管理和共识指南现已制定 可用的。因此，返回具有临床影响力并得到多项支持的目标 PGx 结果 国家和国际协会提供了一个可用于发展生物伦理学的机会 LLFS 中偶然遗传结果返回的框架。我们提议在美国一个现场中心进行试点研究 （匹兹堡大学）证明返回有限 PGx 结果的可行性和可接受性 向 200 名 LLFS 参与者提供三个基因。我们建议在三种药物中鉴定出十种可进行医学操作的 PGx 变体 LLFS 中已有的 WGS 数据中的基因（CYP2C9、CYP2C19 和 VKORC1）。我们将确认 在 CLIA 认证的实验室中观察到的变异，创建一份报告，总结已识别的变异和 受这些变异影响的药物，并建立一项针对研究的 PGx 咨询服务来讨论 根据需要与 LLFS 参与者一起研究结果。我们建议确定参与者评估的理解力， 决策制定以及对两个时间点（立即和三个）返回 PGx 结果（目标 1）的满意度 返回 PGx 结果后几个月。此外，我们将利用 LLFS 队列的家庭结构 评估指数参与者是否与家人分享他们的 PGx 结果并确定 家庭成员对 PGx 结果返回给家庭成员的理解、决策和满意度 指数研究参与者在返回 PGx 结果后 3 个月进行一次电话调查（目标 2）。最后，我们还将评估药剂师/医生确定的 PGx 结果对药物的影响 LLFS 参与者确定药剂师评估和参与者评估的影响之间的任何差距 PGx 结果（目标 2）。在这个项目结束时，我们将解决围绕 将附带的 PGx 结果返回给研究参与者并生成试点数据以支持更广泛的研究 将具有医学意义的偶然遗传发现返回给研究参与者。