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 植入前基因检测（PGT）已被用于多年，以避免胚胎植入 具有罕见的单基因致病等位基因或非整倍性。然而，最近在复杂性状方面的进展 遗传学，再加上从单细胞输入产生准确的全基因组基因型的技术能力， 使得对胚胎进行基因筛查以发现常见的多基因特征和疾病风险成为可能。而 大众媒体提出了“设计婴儿”的幽灵，私营企业已经开始提供 值得怀疑的优点，很少有实证工作已经做了量化多基因胚胎筛选（PES）的效用， 研究其道德影响，并评估持份者的观点。与传统的PGT不同，多基因 风险评分本质上是概率性的和多方面的。PES固有的模糊性需要仔细 考虑，以便临床医生，政策制定者和公众做出明智的决定， 实施多基因胚胎筛查的潜在后果。此外，虽然研究 在过去的几年里，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）生态系统服务费用支付制度在下列情况下产生预期结果的潜在能力 各种现实世界的情况;或2）在潜在的临床一线临床医生的观点和态度 多基因风险评分的应用，特别是在产前背景下。 为了建立一个初步框架，以考虑道德、法律的和社会影响， （ELSI）的PES，有必要建立两套经验参数：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;第二， 和观点的临床医生谁将在第一线管理PES，包括遗传 咨询师、生殖内分泌学家和产科医生。因此，拟议的研究旨在量化 生态系统服务费用支付在不同条件下减少疾病风险的现实结果范围， 模拟和真实的数据的组合。我们还旨在了解临床医生的观点， 可能提供PES，使用深入访谈和生殖临床医生的大规模调查， 遗传学家在拟议的研究项目中，这两个目标将相互交织，相互促进; 统计调查将以利益攸关方提出的关切和问题为指导， 访谈和调查将由我们从统计和方法学的理解， 分析。根据我们的研究结果，我们将对这一快速发展的技术进行伦理分析。