PRS Center for Admixed Populations and Health Equity (CAPE)

PRS 混合人口和健康公平中心 (CAPE)

• 批准号: 10424501
• 负责人: Eimear Elizabeth Kenny
• 金额: $ 97.38万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-08 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10424501
• 关键词: Address; Admixture; African American population; African ancestry; Americas; Asian ancestry; Awareness; Benchmarking; Calibration; Clinical Data; Cohort Studies; Colorado; Complex; Data; Data Set; Databases; Development; Disease; East Asian; Electronic Health Record; Environmental Risk Factor; Epidemiology; Ethnic Origin; European; Event; Gene Expression; Genetic; Genetic Determinism; Genetic Drift; Genetic Models; Genetic Variation; Genetic study; Genome; Genomic medicine; Genomics; Genotype; Health system; Heterogeneity; Hispanic Americans; Human; Incidence; Individual; Jackson Heart Study; Link; Location; Longitudinal cohort; Maps; Medical; Medicine; Methods; Mexican Americans; Modeling; Molecular; Mosaicism; Participant; Patient Self-Report; Population; Population Genetics; Process; Proxy; Puerto Rican; Race; Relative Risks; Research; Risk; Risk Factors; Sample Size; Slave; Socioeconomic Status; Source; Statistical Methods; Structure; System; Testing; Uncertainty; Variant; World Health; base; biobank; causal variant; cohort; data harmonization; digital health; disease natural history; genetic architecture; genome-wide; genomic data; health data; health equity; health management; improved; interest; novel; patient population; phenotypic data; polygenic risk score; population based; population health; portability; social health determinants; tool; trait; transcriptome; urban setting

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.

项目概要/摘要 多基因风险评分 (PRS) 汇总了基因组中常见变异的风险，已成为一种评估风险的方法。 实施基因组医学的强大工具。不幸的是，绝大多数基因组数据来自 目前估计的 PRS 来自欧洲血统个体，因此禁止 为非欧洲个人实施 PRS。为了解决这一差距，多个大规模基因组 目前正在非欧洲个体中进行研究。特别感兴趣的是最近有 来自多个大陆的血统，例如非洲裔美国人和/或西班牙裔美国人 基因组是不同祖先片段的镶嵌体。遗传祖先的这种多样性产生了独特的 由于现有 PRS 的准确性和偏差因基因组而异，因此公平 PRS 开发面临挑战 祖先。与主要将遗传血统视为 PRS 研究中的混杂因素的现有范式不同，我们 旨在充分整合混合过程的群体遗传学，以产生混合-PRS，从而提供 无论遗传血统如何，所有个体都具有公平的准确性。我们将整合超过23万条数据 混合了五个不同医疗系统（包括加州大学洛杉矶分校、西奈山、科罗拉多州）的个人来开发， 为混合个体校准和基准 PRS。