Facilitating Implementation Science within the SIBS Genomics Study (SIBS-Gen-Gen)

促进SIBS基因组学研究（SIBS-Gen-Gen）中的实施科学 项目摘要 中风是长期残疾的主要原因，仍然是全球第二大常见死因 非洲血统的人负担最重。中风是一种复杂的特征， 基因贡献虽然MEGASTROKE在其他研究中发现了缺血性卒中的某些遗传变异， 不包括土著非洲人（IA）的人群，卒中研究中的候选基因研究 研究和教育网络（SIREN）已经报道了一些位点，我们正在进行第一次 一项全基因组关联研究揭示了土著非洲人中风的遗传决定因素 在使用基因组学（SIBS基因组学）研究（R 01- NS107900）。 虽然已确定的风险因素（如高血压）的评估结果被披露为无中风， 对于个体而言，在转化为实践之前，验证其新兴的遗传决定因素至关重要 社区此外，探讨披露基因测试结果的影响也至关重要 中风患者及其家庭成员。伦理、临床和社会影响 披露多基因性状的临床重要遗传决定因素的基因检测结果， 作为中风，在IA中尚未被表征。翻译SIREN即将和未来的调查结果 和SIBS基因组学研究通过实施科学进入临床和社区服务，它是 重要的是要了解无中风患者对披露的看法、偏好和态度 中风的基因结果 因此，使用行政补充机制响应NOT-TW-19-003，我们将 对SIB-基因组学（R 01-NS 107900）进行一项称为SIBS基因组学-遗传学的辅助研究 咨询（SIBS-Gen-Gen），以便准备将其调查结果推广到实践和人口。 我们将调查无中风个体对披露信息的感知、偏好和态度， 中风基因检测的结果，同时建设披露结果和基因的能力， 中风咨询我们将探讨不同层次的临床效用的遗传变异使用 创新扩散理论在社会生态模型的几个层面上探讨这些问题：a） 个体：427例无卒中对照; B）其家人/重要他人; c）医疗保健提供者和d） 社区 我们还将举办一个遗传咨询讲习班，培训研究助理、研究人员， 医疗保健提供者和SIBS Genomics的社区参与工作人员就结果的披露 与中风/多基因风险评分相关的经验证的致病性遗传变异;以及如何处理 非致病性结果和未知意义的变体。这项研究将为以下方面提供试点数据： 设计一项关于披露中风基因检测结果的随机对照试验。

Facilitating Implementation Science within the SIBS Genomics Study (SIBS-Gen-Gen) PROJECT SUMMARY Stroke, a leading cause of long-term disability, is still the second most common cause of death globally with its highest burden among people of African ancestry. Stroke is a complex trait with substantial genetic contribution. While MEGASTROKE identified certain genetic variants for ischemic stroke in other populations excluding indigenous Africans (IA), candidate gene studies within the Stroke Investigative Research and Education Network (SIREN) have reported some loci, and we are conducting the first genome-wide association study to unravel genetic determinants of stroke among indigenous Africans within the Systematic Investigation of Blacks with Stroke using Genomics (SIBS Genomics) study (R01- NS107900). While results of assessment of established risk factors such as hypertension is disclosed to stroke-free individuals, it is critical to validate its emerging genetic determinants before translation to practice community. Moreover, it is crucial to explore the implications of disclosure of the results of genetic test for stroke to stroke-free individuals and their family members. The ethical, clinical, and social implications of disclosure of genetic test results for clinically significant genetic determinants of polygenic traits such as stroke, has not been characterized among IA. To translate imminent and future findings from SIREN and SIBS Genomics studies into clinical and community services through implementation science, it is important to understand stroke-free individuals’ perception, preferences and attitude towards disclosure of genetic results for stroke. Therefore, using the administrative supplement mechanism in response to NOT-TW-19-003, we will conduct an ancillary study to SIB-Genomics (R01-NS107900) called SIBS Genomics-Genetic counselling (SIBS-Gen-Gen) to prepare for generalization of its findings to practice and the population. We will investigate stroke-free individuals’ perception, preferences and attitudes towards disclosure of results of genetic testing for stroke while building capacity for disclosure of results and genetic counselling for stroke. We will explore the various tiers of clinical utility of genetic variants using the diffusion of innovations theory to explore these at several levels of the socio-ecological model: a) individual: 427 stroke-free controls; b) their family/significant others; c) healthcare providers and d) community. We will also conduct a workshop on genetic counseling to train the research assistants, investigators, healthcare providers, and community engagement staff of SIBS Genomics on the disclosure of results of validated pathogenic genetic variants associated with stroke/polygenic risk score; and how to handle non-pathogenic results and variants of unknown significance. This study will provide pilot data for designing a randomized controlled trial on disclosure of stroke genetic tests results.