Polygenic Risk of Disease in Populations of Diverse Ancestry

不同血统人群的多基因疾病风险

基本信息

批准号：
10670372
负责人：
Iftikhar J Kullo
金额：
$ 60.41万
依托单位：
MAYO CLINIC ROCHESTER
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：
2021-09-08 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10670372
关键词：
Address Admixture Adult All of Us Research Program Categories Classification Clinical Collaborations Complex Computing Methodologies Coronary heart disease Data Data Element Data Set Development Diabetes Mellitus Disease East Asian Electronic Health Record Electronic Medical Records and Genomics Network Ensure Equation Equity European ancestry Gene Frequency Generations Genetic Genetic Diseases Genetic Variation Genomic medicine Genotype Goals Grant Health Heritability Hypertension Individual International Linkage Disequilibrium Metadata Methods Middle Eastern Modeling Obesity Ontology Outcome Pattern Performance Phase Phenotype Population Population Genetics Population Heterogeneity Prevention Public Health Risk Risk Estimate Risk Factors Sample Size Site Source South Asian Statistical Methods Testing Therapeutic Variant Veterans Weight Work biobank clinic ready clinical decision-making clinical practice clinical risk cloud platform cohort data harmonization data integration data modeling data standards database of Genotypes and Phenotypes disorder risk genome wide association study genomic data health disparity heart disease risk hypercholesterolemia improved innovation large datasets novel phenotypic data polygenic risk score precision medicine programs randomized, clinical trials risk prediction risk stratification risk variant statistics working group

项目摘要

PROJECT SUMMARY In this application we propose to build on our prior work on polygenic risk scores (PRSs) to extend these to diverse ancestry groups. By improving risk stratification, PRSs for common diseases have the potential to transform clinical practice. However, such PRSs must be available for diverse ancestry groups to ensure equitable implementation of genomic medicine and reduce the potential exacerbation of health disparities in the context of genomic medicine. Our application aims to address the critical need to develop PRSs for diverse ancestry groups and will focus on coronary heart disease (CHD) and its risk factors: hypertension, diabetes, obesity and hypercholesterolemia, collectively an enormous health burden world-wide. CHD is the prototypical complex disease for the use of PRSs given available validated risk prediction equations that bin individuals into risk categories and substantial reclassification across these categories by a PRS with consequent therapeutic implications. As part of the PRS Diversity Consortium (PRS-DC), we will develop methods to generate PRSs for populations of diverse ancestry using existing and new datasets with genomic and phenotype data for CHD and its risk factors. We will harmonize data elements across these data sets. The methods we develop will be applicable towards the generation of PRSs for a broad range of common diseases across diverse populations. The investigative team is part of the Mayo eMERGE IV application and will serve as a bridge between the PRS-DC and eMERGE. To generate PRSs for diverse ancestries, we will use data from the eMERGE consortium, Million Veteran’s Program (MVP), the All of US (AoU) program, dbGAP, PRS-DC sites, UK Biobank, and collaborations with several international groups representing the Middle Eastern, South Asian and East Asian cohorts. Our application includes several innovations to enable the use of PRSs for risk stratification and prevention of CHD in individuals belonging to diverse ancestries. Our specific aims are: Specific aim 1. Integrate and harmonize phenotype data from heterogeneous sources to enable cross platform phenotyping and generation of PRSs for common diseases in diverse ancestry groups. Specific aim 2. Develop PRSs for CHD and its major risk factors (hypertension, diabetes, obesity, hypercholesterolemia) in populations of diverse ancestry. Specific aim 3. Develop novel statistical and computational methods to account for diverse genetic ancestry and admixture in models of polygenic risk. Specific aim 4. Develop ‘clinic ready’ PRSs for diverse ancestry groups by creating reference distributions of a PRSCHD and integrate it with clinical information to compute absolute risk estimates.

项目摘要在此应用程序中，我们建议以我们先前在多基因风险分数（PRS）为基础的工作中扩展到这些工作潜水血统群体。通过改善风险分层，普通疾病的PRS有可能改变临床实践。但是，这样的PRS必须适合潜水祖先以确保公平的基因组医学实施，并减少健康分布的潜在加剧基因组医学的背景。我们的申请旨在满足为潜水员开发PRS的关键需求祖先，将关注冠心病（CHD）及其危险因素：高血压，糖尿病，肥胖和高胆固醇血症，全球范围内总体健康。冠心病是原型的使用PRS的复杂疾病给定可用的经过验证的风险预测方程随之而来的治疗含义。作为PRS多样性财团（PRS-DC）的一部分，我们将开发生成PRS的方法对于使用现有和新数据集的多样性血统群体，具有基因组和表型数据的冠心病及其风险因素。我们将在这些数据集中协调数据元素。我们开发的方法将是适用于在潜水员种群中广泛的普通疾病的生成PRS。调查团队是Mayo Emerge IV应用的一部分，将作为 PRS-DC和出现。为了为潜水员生成PRS，我们将使用来自Emerge的数据财团，百万退伍军人计划（MVP），我们所有人（AOU）计划，DBGAP，PRS-DC网站，英国，英国生物库，以及与代表中东，南亚的几个国际团体合作和东亚人群。我们的申请包括几项创新，以实现PRS的风险属于潜水祖先的个体的分层和预防冠心病。我们的具体目的是：特定目的1。从异质来源整合和协调表型数据以启用跨平台在潜水祖先的常见疾病群体中的表型和生成PRS。具体目标2。冠心病及其主要危险因素（高血压，糖尿病，肥胖，高胆固醇血症）的PRSS 潜水血统。特定目的3。开发新颖的统计和计算方法来说明潜水员的遗传血统和多基因风险模型中的混合物。特定目标4。开发“诊所就绪” PRS 通过创建PRSCHD的参考分布并将其与临床整合在一起，以实现多样性祖先组信息以计算绝对风险估计。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Use of Polygenic Risk Scores for Coronary Heart Disease in Ancestrally Diverse Populations.

DOI：
10.1007/s11886-022-01734-0
发表时间：
2022-09
期刊：
CURRENT CARDIOLOGY REPORTS
影响因子：
3.7
作者：
Dikilitas, Ozan;Schaid, Daniel J.;Tcheandjieu, Catherine;Clarke, Shoa L.;Assimes, Themistocles L.;Kullo, Iftikhar J.
通讯作者：
Kullo, Iftikhar J.

Implementing Reporting Standards for Polygenic Risk Scores for Atherosclerotic Cardiovascular Disease.