Polygenic Embryo Screening: Towards Informed Decision-Making

多基因胚胎筛查：做出明智的决策

• 批准号: 10414053
• 负责人: SHAI CARMI
• 金额: $ 72.3万
• 依托单位: FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10414053
• 关键词: Alleles; Aneuploidy; Assisted Reproductive Technology; Attitude; Cells; Complex Genetic Trait; Confidence Intervals; Coupled; Data; Data Set; Decision Making; Diabetes Mellitus; Disease; Embryo; Endocrinologist; Ethical Analysis; Ethics; Future; General Population; Genotype; Heart Diseases; Height; Individual; Industry; Intelligence; Interview; Investigation; Knowledge; Malignant Neoplasms; Mendelian disorder; Mental disorders; Methodology; Modeling; Motivation; Noise; Outcome; Partner in relationship; Patients; Phase; Polygenic Traits; Preimplantation Diagnosis; Prevalence; Privatization; Property; Publishing; Reporting; Reproductive Medicine; Research; Research Project Grants; Risk; Risk Reduction; Screening procedure; Services; Shapes; Stigmatization; Surveys; Technology; Time; Uncertainty; Work; base; clinical application; design; disorder risk; ethical legal social implication; evidence base; genetic counselor; genome-wide; interest; natural Blastocyst Implantation; pleiotropism; polygenic risk score; preference; prenatal; reproductive; screening; simulation; stakeholder perspectives; theories; trait; willingness

PROJECT SUMMARY Preimplantation genetic testing (PGT) has been utilized for years to avoid implantation of embryos harboring rare monogenic disease-causing alleles or aneuploidies. However, recent progress in complex trait genetics, coupled with the technical ability to generate accurate genome-wide genotypes from single-cell input, has made it possible to genetically screen embryos for common polygenic traits and disease risk. While popular media has raised the specter of ‘‘designer babies,’’ and private industry has begun to offer services of dubious merit, little empirical work has been done to quantify the utility of polygenic embryo screening (PES), examine its ethical implications, and assess stakeholders’ perspectives. Unlike conventional PGT, polygenic risk scores are intrinsically probabilistic and multifaceted. The inherent ambiguities of PES requires careful consideration in order for clinicians, policymakers, and the general public to make informed decisions about the potential consequences of implementing polygenic embryo screening. Moreover, although research momentum for polygenic risk scores has grown exponentially in the last few years, there is almost no independent, empirical data on either: 1) the potential ability of PES to produce desired outcomes under various real-world scenarios; or 2) the perspectives and attitudes of front-line clinicians in the potential clinical application of polygenic risk scores, especially in the prenatal context. In order to build an initial framework for the consideration of the ethical, legal, and social implications (ELSI) of PES, it is necessary to establish two sets of empirical parameters: first, the statistical properties that will shape the potential application of polygenic risk scores in the prenatal setting; and second, the attitudes and perspectives of clinicians who would be at the front lines of administering PES, including genetic counselors, reproductive endocrinologists, and obstetricians. The proposed study therefore aims to quantify the range of realistic outcomes of PES in the context of disease risk reduction under varying conditions, using a combination of simulated and real data. We also aim to understand the perspectives of clinicians who would potentially deliver PES, using both in-depth interviews and a large-scale survey of reproductive clinicians and geneticists. In the proposed research project, these two aims will be interdigitated and mutually informative; statistical investigation will be guided by concerns and questions posed by stakeholders, and stakeholder interviews and surveys will be shaped by the statistical and methodological understanding obtained from our analyses. On the basis of our results, we will perform ethical analysis of this rapidly evolving technology.

项目摘要 多年来，现有遗传测试（PGT）已被用来避免植入胚胎 具有罕见的致病等位基因或非整倍性。但是，复杂性状的最新进展 遗传学，再加上从单细胞输入中生成精确全基因组基因型的技术能力， 已经使遗传胚胎具有常见的多基因性状和疾病风险成为可能。尽管 流行媒体培养了``设计师婴儿''的幽灵，私营企业已开始提供 可疑的优点，几乎没有实证工作来量化多基因胚胎筛选（PES）的实用性， 检查其道德意义，并评估利益相关者的观点。与常规PGT不同，多基因 风险评分本质上是概率和多方面的。 PE的继承歧义需要仔细 考虑临床医生，政策制定者和公众，以做出明智的决定 实施多基因胚胎筛选的潜在后果。而且，尽管研究 多基因风险分数的动力在过去几年中成倍增长，几乎没有 关于以下任一的独立的经验数据：1）PE在下面产生预期结果的潜在能力 各种真实的场景；或2）潜在临床的一线临床医生的观点和参与 多基因风险评分的应用，尤其是在产前背景下。 为了建立一个初始框架，以考虑道德，法律和社会影响 （Elsi）PES，必须建立两组经验参数：首先，统计属性 将在产前环境中塑造多基因风险评分的潜在应用；其次，态度 以及将处于管理PE的前线的临床医生的观点，包括遗传 男性，生殖内分泌学家和产科医生。因此，拟议的研究旨在量化 在不同条件下疾病风险降低的背景下，PE的现实结果的范围 模拟和真实数据的组合。我们还旨在了解临床医生的观点 使用深入的访谈和对复制临床医生和 仿制药。在拟议的研究项目中，这两个目标将被互连并相互提供信息。 统计调查将以利益相关者和利益相关者的关注和问题为指导 访谈和调查将由我们从我们的统计和方法论理解来塑造 分析。根据我们的结果，我们将对这项快速发展的技术进行道德分析。