PRS Center for Admixed Populations and Health Equity (CAPE)

项目总结/摘要 多基因风险评分（PRS），即基因组中常见变异的风险汇总，已成为一种新的风险评估方法。 这是实现基因组医学的有力工具。不幸的是，绝大多数来自 据估计，目前的PRS来自欧洲血统的个人，因此禁止 对非欧洲人实施减贫战略。为了解决这一差距，多个大规模的基因组 目前的研究是在非欧洲人中进行的。特别感兴趣的是最近 来自多个大陆来源的祖先，如非洲裔美国人和/或西班牙裔美国人， 基因组是不同祖先片段的镶嵌体。这种遗传祖先的多样性， 由于现有PRS的准确性和偏差在基因组之间存在差异，因此公平PRS开发面临挑战 祖先不像现有的范式，在很大程度上认为遗传祖先作为一个混杂因素，在PRS研究，我们 目的是充分整合混合过程的群体遗传学，以产生提供 公平的准确性，所有个人，无论遗传祖先。我们将整合超过23万的数据 混合了五个不同医疗系统的个人，包括加州大学洛杉矶分校、西奈山、科罗拉多， 为混合个体校准和基准PRS。

Project Summary/Abstract Polygenic risk scores (PRS), that aggregate risk across common variants in the genome, have emerged as a powerful tool towards implementing genomic medicine. Unfortunately, the vast majority of genomic data from which current PRS are estimated is coming from European ancestry individuals thus prohibiting the implementation of PRS for non-European individuals. To address this gap, multiple large-scale genomic studies are currently performed in non-European individuals. Of particular interest are individuals with recent ancestry from multiple continental sources such as African Americans and/or Hispanic Americans whose genomes are a mosaic of segments of various ancestries. Such diversity in genetic ancestry raises unique challenges in the equitable PRS development as the accuracy and bias of existing PRS varies across genomic ancestries. Unlike existing paradigm that largely views genetic ancestry as a confounder in PRS studies, we aim to fully integrate population genetics of the admixture process to yield admixture-PRS that provide equitable accuracies for all individuals irrespective of genetic ancestries. We will integrate data of over 230,000 admixed individuals across five diverse medical systems including UCLA, Mt Sinai, Colorado to develop, calibrate and benchmark PRS for admixed individuals.