Polygenic risk scores and health disparities: the role of blood cells immune response and evolutionary adaptation

多基因风险评分和健康差异:血细胞免疫反应和进化适应的作用

基本信息

  • 批准号:
    10212768
  • 负责人:
  • 金额:
    $ 99.99万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 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

项目摘要

Abstract The large number of disease susceptibility loci identified from genome-wide association studies (GWAS) is enabling polygenic risk scores (PRS) to deliver on their promise to improve health outcomes and to transform the practice of personalized medicine. The reduced quality of PRS for common diseases and related quantitative traits for populations of recent African, Asian, and Native American ancestries relative to those for populations of recent European ancestries, however, threatens to create a new class of disparities in the delivery of healthcare based on PRS. The number of individuals of non-European ancestry with genome interrogation are growing much more rapidly now than 5 years ago; nevertheless, the number of individuals of recent European ancestries with genome interrogation grows still more rapidly and it is likely to be many years before sample sizes for genome interrogation in even major continental groups are close to proportional to relative population sizes. Thus, it is critical to optimize PRS performance for diverse populations in as many ways as we can. Given the substantial and growing fraction of the US population with genomes admixed from different continental ancestries, we believe that high quality PRS for much of the US population is unlikely to be achieved without properly accounting for local ancestries. Similarly, focused strategies to identify high-impact but population-specific variants could improve the quality of PRS in populations with such alleles. DNA variants from regions with a signature of natural selection often demonstrate such properties, and have been shown to be enriched among top associations for a number of hematological and immune/inflammatory traits that are important biomarkers for key chronic diseases. We propose to focus our PRS studies on hematological and immune/inflammatory traits and their associated chronic diseases and to extend methods for the development of PRS to accommodate estimates of local ancestry, high impact population-specific variants and multiple endophenotypes. Thus, our Specific Aims are: 1) Assemble and harmonize data sets needed to accomplish the goals of the project, including hematological traits (red blood cell, white blood cell, platelet), and immune/inflammatory traits (CRP, fibrinogen, D-dimer) from: Jackson Heart Study, Women’s Health Initiative, BioVU, and GeneSTAR. 2) Extend PRS methods to: a) explicitly model local ancestry; b) accommodate large-effect but population-specific risk alleles (such as those from regions with a signature of natural selection); and c) enable joint modeling of multiple endophenotypes; and 3) Develop and apply novel PRS and overall disease prediction models to: a) estimate risk of common diseases and related biomarkers affected by hematological, thrombotic and immune/inflammatory biology; and b) enable calculation of PRS-adjusted clinical laboratory values to reduce structural health disparities.
摘要 从全基因组关联研究中确定的大量疾病易感基因座是 使多基因风险评分(PR)能够兑现其改善健康结果和转变的承诺 个性化医疗的实践。常见病及相关疾病诊断报告质量下降 现代非洲人、亚洲人和美洲原住民祖先的数量性状相对于 然而,最近的欧洲祖先的种群有可能在 基于PRS的医疗服务的提供。具有基因组的非欧洲血统的个体数量 审问现在比5年前增长得快得多;然而, 最近的欧洲祖先对基因组的询问发展得更快,很可能需要很多年 在此之前,即使是主要大陆群体的基因组询问样本大小也接近于 相对人口规模。因此,在AS中优化不同人群的PRS性能是至关重要的 尽我们所能用很多方法。鉴于美国人口中携带基因组的比例很大,而且还在不断增长 混杂着来自不同大陆祖先的人,我们相信对于大部分美国人来说,高质量的PR 如果不适当考虑当地的祖先,就不太可能实现这一目标。同样,有重点的战略可以 识别高影响但特定于人群的变异可能会改善患有这种疾病的人群的PR质量 等位基因。来自具有自然选择特征的区域的DNA变体通常表现出这样的特性,并且 已被证明在许多血液学和血液学的顶级关联中富含 免疫/炎症特征是关键慢性病的重要生物标志物。我们建议集中我们的 血液学和免疫/炎症特征及其相关慢性病的PRS研究 扩展PR的开发方法以适应当地祖先的估计,影响很大 群体特有的变异和多种内表型。因此,我们的具体目标是:1)组装和 协调完成项目目标所需的数据集,包括血液学特征(RED 血细胞、白细胞、血小板)和免疫/炎症特征(C反应蛋白、纤维蛋白原、D-二聚体),来自:Jackson 心脏研究、妇女健康倡议、BioVU和GeneSTAR。2)将PRS方法扩展为:a)显式 模范当地血统;b)适应大效应但特定于人群的风险等位基因(如 来自具有自然选择特征的区域);以及c)允许对多个 内表型;以及3)开发和应用新的PRS和整体疾病预测模型:a) 评估常见疾病和相关生物标记物受血液病、血栓形成和 免疫/炎症生物学;以及b)能够计算经PRS调整的临床化验值以 缩小结构性健康差距。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Nancy J Cox其他文献

Reaching for the next branch on the biobank tree of knowledge
伸手去够生物银行知识之树上的下一个分支
  • DOI:
    10.1038/ng.3946
  • 发表时间:
    2017-09-01
  • 期刊:
  • 影响因子:
    29.000
  • 作者:
    Nancy J Cox
  • 通讯作者:
    Nancy J Cox

Nancy J Cox的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Nancy J Cox', 18)}}的其他基金

FIGOR: Fellowship In Genomics Outcomes Research
FigOR:基因组结果研究奖学金
  • 批准号:
    10628304
  • 财政年份:
    2023
  • 资助金额:
    $ 99.99万
  • 项目类别:
Training Program on Genetic Variation and Human Phenotypes
遗传变异和人类表型培训计划
  • 批准号:
    10420390
  • 财政年份:
    2022
  • 资助金额:
    $ 99.99万
  • 项目类别:
Training Program on Genetic Variation and Human Phenotypes
遗传变异和人类表型培训计划
  • 批准号:
    10651837
  • 财政年份:
    2022
  • 资助金额:
    $ 99.99万
  • 项目类别:
Southeast Collaborative for Innovative and Equitable Solutions to Chronic Disease Disparities
东南合作以创新和公平的方式解决慢性病差异
  • 批准号:
    10891968
  • 财政年份:
    2021
  • 资助金额:
    $ 99.99万
  • 项目类别:
Polygenic risk scores and health disparities: the role of blood cells immune response and evolutionary adaptation
多基因风险评分和健康差异:血细胞免疫反应和进化适应的作用
  • 批准号:
    10424445
  • 财政年份:
    2021
  • 资助金额:
    $ 99.99万
  • 项目类别:
Southeast Collaborative for Innovative and Equitable Solutions to Chronic Disease Disparities
东南合作以创新和公平的方式解决慢性病差异
  • 批准号:
    10437309
  • 财政年份:
    2021
  • 资助金额:
    $ 99.99万
  • 项目类别:
Southeast Collaborative for Innovative and Equitable Solutions to Chronic Disease Disparities
东南合作以创新和公平的方式解决慢性病差异
  • 批准号:
    10657748
  • 财政年份:
    2021
  • 资助金额:
    $ 99.99万
  • 项目类别:
Southeast Collaborative for Innovative and Equitable Solutions to Chronic Disease Disparities
东南合作以创新和公平的方式解决慢性病差异
  • 批准号:
    10494158
  • 财政年份:
    2021
  • 资助金额:
    $ 99.99万
  • 项目类别:
Polygenic risk scores and health disparities: the role of blood cells immune response and evolutionary adaptation
多基因风险评分和健康差异:血细胞免疫反应和进化适应的作用
  • 批准号:
    10613573
  • 财政年份:
    2021
  • 资助金额:
    $ 99.99万
  • 项目类别:
Southeast Collaborative for Innovative and Equitable Solutions to Chronic Disease Disparities
东南合作以创新和公平的方式解决慢性病差异
  • 批准号:
    10604586
  • 财政年份:
    2021
  • 资助金额:
    $ 99.99万
  • 项目类别:

相似海外基金

Unraveling the Dynamics of International Accounting: Exploring the Impact of IFRS Adoption on Firms' Financial Reporting and Business Strategies
揭示国际会计的动态:探索采用 IFRS 对公司财务报告和业务战略的影响
  • 批准号:
    24K16488
  • 财政年份:
    2024
  • 资助金额:
    $ 99.99万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Mighty Accounting - Accountancy Automation for 1-person limited companies.
Mighty Accounting - 1 人有限公司的会计自动化。
  • 批准号:
    10100360
  • 财政年份:
    2024
  • 资助金额:
    $ 99.99万
  • 项目类别:
    Collaborative R&D
Accounting for the Fall of Silver? Western exchange banking practice, 1870-1910
白银下跌的原因是什么?
  • 批准号:
    24K04974
  • 财政年份:
    2024
  • 资助金额:
    $ 99.99万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
A New Direction in Accounting Education for IT Human Resources
IT人力资源会计教育的新方向
  • 批准号:
    23K01686
  • 财政年份:
    2023
  • 资助金额:
    $ 99.99万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
An empirical and theoretical study of the double-accounting system in 19th-century American and British public utility companies
19世纪美国和英国公用事业公司双重会计制度的实证和理论研究
  • 批准号:
    23K01692
  • 财政年份:
    2023
  • 资助金额:
    $ 99.99万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
An Empirical Analysis of the Value Effect: An Accounting Viewpoint
价值效应的实证分析:会计观点
  • 批准号:
    23K01695
  • 财政年份:
    2023
  • 资助金额:
    $ 99.99万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Accounting model for improving performance on the health and productivity management
提高健康和生产力管理绩效的会计模型
  • 批准号:
    23K01713
  • 财政年份:
    2023
  • 资助金额:
    $ 99.99万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
CPS: Medium: Making Every Drop Count: Accounting for Spatiotemporal Variability of Water Needs for Proactive Scheduling of Variable Rate Irrigation Systems
CPS:中:让每一滴水都发挥作用:考虑用水需求的时空变化,主动调度可变速率灌溉系统
  • 批准号:
    2312319
  • 财政年份:
    2023
  • 资助金额:
    $ 99.99万
  • 项目类别:
    Standard Grant
New Role of Not-for-Profit Entities and Their Accounting Standards to Be Unified
非营利实体的新角色及其会计准则将统一
  • 批准号:
    23K01715
  • 财政年份:
    2023
  • 资助金额:
    $ 99.99万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Improving Age- and Cause-Specific Under-Five Mortality Rates (ACSU5MR) by Systematically Accounting Measurement Errors to Inform Child Survival Decision Making in Low Income Countries
通过系统地核算测量误差来改善特定年龄和特定原因的五岁以下死亡率 (ACSU5MR),为低收入国家的儿童生存决策提供信息
  • 批准号:
    10585388
  • 财政年份:
    2023
  • 资助金额:
    $ 99.99万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了