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.

项目概要 植入前基因检测 (PGT) 多年来一直用于避免胚胎植入 含有罕见的单基因致病等位基因或非整倍体然而，复杂性状的最新进展。 遗传学，加上从单细胞输入生成准确的全基因组基因型的技术能力， 使得对胚胎常见的多基因性状和疾病风险进行基因筛查成为可能。 大众媒体引发了“设计婴儿”的担忧，私营企业已开始提供 值得怀疑的是，很少有实证工作来量化多基因胚胎筛选（PES）的效用， 与传统的 PGT 不同，多基因技术检查其伦理影响，并评估利益相关者的观点。 风险评分本质上是概率性的和多方面的 PES 固有的模糊性需要谨慎对待。 以便赞助人、政策制定者和公众就该问题做出明智的决定 实施多基因胚胎筛选的潜在后果。 过去几年，多基因风险评分的势头呈指数级增长，几乎没有 独立的经验数据：1）PES 在以下情况下产生预期结果的潜在能力： 各种现实世界场景；或 2) 潜在临床中一线防御者的观点和态度 多基因风险评分的应用，特别是在产前环境中。 为了建立一个考虑伦理、法律和社会影响的初步框架 （ELSI）PES，需要建立两组经验参数：第一，统计特性 将塑造多基因风险评分在产前环境中的潜在应用；其次，态度； 以及处于 PES 管理第一线的主教的观点，包括遗传 因此，拟议的研究旨在量化咨询师、生殖内分泌学家和产科医生。 在不同条件下降低疾病风险的情况下 PES 的实际结果范围，使用 我们还希望结合模拟数据和真实数据来了解防守者的观点。 通过深入访谈和对生殖和生殖系统的大规模调查，有可能提供 PES 在拟议的研究项目中，这两个目标将相互交叉且相互提供信息； 统计调查将以利益相关者和利益相关者提出的关切和问题为指导 访谈和调查将根据我们从统计和方法论中获得的理解来制定 根据我们的结果，我们将对这项快速发展的技术进行伦理分析。