PRS Center for Admixed Populations and Health Equity (CAPE)

项目摘要/摘要 多基因风险分数(PR)，即基因组中常见变异的综合风险，已成为一种 实施基因组医学的有力工具。不幸的是，绝大多数基因组数据来自 据估计，目前的PR来自欧洲血统的个人，因此禁止 为非欧洲人实施了减贫战略。为了弥补这一差距，多个大规模基因组 研究目前是在非欧洲人身上进行的。特别令人感兴趣的是最近 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，他们 基因组是不同祖先的片段的马赛克。这种遗传祖先的多样性带来了独特的 由于现有PR的准确性和偏倚在基因组中各不相同，因此公平的PR开发面临挑战 祖先。与现有范式在很大程度上将遗传祖先视为PR研究中的混杂因素不同，我们 目的充分整合群体遗传学的混合过程，以产生混合-PR，从而提供 对于所有个体，不论其遗传祖先如何，都具有同等的精确度。我们将整合超过23万个数据 包括加州大学洛杉矶分校、西奈山、科罗拉多州在内的五个不同医疗系统的混合个体开发， 为混杂的个人校准和基准PR。

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.