Polygenic Risk Score (PRS) Methods and Analysis for Populations of Diverse Ancestry - Study Sites

不同血统人群的多基因风险评分 (PRS) 方法和分析 - 研究地点

基本信息

批准号：
10610936
负责人：
Sally Nneoma Adebamowo
金额：
$ 93.52万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
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

来源：
https://reporter.nih.gov/project-details/10610936
关键词：
Admixture Affect Africa African African American African American population African ancestry Algorithms Alleles American Biological Blood Pressure Body mass index Cardiometabolic Disease Cardiovascular Diseases Cause of Death Chronic Disease Clinical Management Cohort Studies Communicable Diseases Complex Country Creatine Data Data Collection Data Set Development Diabetes Mellitus Diagnosis Disease Dyslipidemias Environment Environmental Risk Factor Ethnic Origin Etiology European European ancestry Funding Gene Frequency Genetic Genetic Risk Genetic Variation Genome Genomic Segment Genomics Genotype Glucose Guidelines Health Health Policy Heart Diseases Heredity Heterogeneity Human Hypertension Individual Insulin Jamaican Joints Kidney Diseases Knowledge Lead Life Style Linkage Disequilibrium Lipids Methods Modeling Morbidity - disease rate North America Northern Africa Obesity Participant Patients Performance Persons Phenotype Population Population Analysis Population Heterogeneity Population Study Prevention strategy Process Protocols documentation Public Health Publications Quality Control Research Resources Risk Risk Factors Scientist Scoring Method Signal Transduction Site Stroke Structure Target Populations Translating Trust United States National Institutes of Health Variant Work burden of illness cardiometabolism clinical risk cohort dashboard data harmonization data integration data standards diagnostic strategy disorder risk diverse data genome wide association study genomic data genomic variation health disparity health inequalities improved insight interactive tool lifestyle data machine learning method member mortality multi-ethnic novel phenotypic data polygenic risk score population stratification prevent tool trait working group

项目摘要

Abstract/Summary Globally, non-communicable diseases (NCDs) outrank infectious diseases in terms of public health burden. Cardiometabolic diseases (CMD) such as heart disease and stroke are the leading causes of death worldwide. In this application we will explore the genomic risk for common CMD, including hypertension, stroke, diabetes, obesity, dyslipidemia and kidney disease, and related traits (including BMI, blood pressure, lipid, glucose, insulin and creatine) across populations with African ancestry (AA). There is evidence to suggest that polygenic risk scores (PRSs) translate poorly from a discovery study in one ancestral population (e.g. European Americans) to a target population (e.g. sub-Saharan Africans), especially when they are separated by large genetic differences. However, this has not been evaluated with large, well-powered AA datasets. Furthermore, the high genetic diversity and population structure among non-European Ancestry (EA) populations need to be investigated to understand the performance of PRSs in other regions populated by people with diverse genomic backgrounds. We bring together the Human Heredity and Health in Africa Consortium (H3Africa), other African, Jamaican and African American core cohorts, to develop a joint resource of over 50,000 participants with relevant phenotype and genomics data, referred to as the CARdiometabolic Disorders IN African-ancestry PopuLations (CARDINAL) Study Site. In addition, the CARDINAL Study Site will include 5 replication cohorts with >100,000 participants from diverse ancestry populations. Our main objective is to establish a Study Site for PRS Methods and Analysis for AA Populations and to collaboratively generate and refine PRS for other populations of diverse ancestry by integrating existing datasets with genomics and phenotype data for a range of complex diseases and traits. Our first aim is to integrate phenotype and genomic datasets from ~50,000 African individuals from seven individual cohort studies. Subsequently, we will evaluate PRSs and develop a novel method that takes into consideration, ancestry-specific genomic regions to improve prediction of PRSs in populations characterised by genetic sub-structure. Finally, we will develop an interactive dashboard for dissemination of PRS-related data from diverse ancestry populations. CARDINAL Study Site is ideal for generating novel biologic insights into complex disease etiology, with applications in global populations. Members of the CARDINAL team have successfully worked together for about a decade, generating and disseminating scientific knowledge through high impact publications. By establishing a Study Site in the Polygenic Risk Score Diversity Consortium, CARDINAL brings the largest cohort of African-ancestry participants to the table, to explore the genomics contribution to common CMDs and other NCDs.

摘要/总结在全球范围内，非传染性疾病（NCD）对公共卫生负担的影响超过了传染病。心脏病和中风等心脏代谢疾病（CMD）是全世界死亡的主要原因。在此应用中，我们将探讨常见 CMD 的基因组风险，包括高血压、中风、糖尿病、肥胖、血脂异常和肾脏疾病以及相关特征（包括BMI、血压、血脂、血糖、胰岛素和肌酸）在非洲血统（AA）人群中的应用。有证据表明多基因风险一项针对某个祖先群体（例如欧洲裔美国人）的发现研究的分数（PRS）很难转化为目标人群（例如撒哈拉以南非洲人），特别是当他们因巨大的遗传差异而分开时。然而，尚未使用大型、功能强大的 AA 数据集对此进行评估。此外，高遗传需要调查非欧洲血统 (EA) 人群的多样性和人口结构了解 PRS 在拥有不同基因组背景的人居住的其他地区的表现。我们汇集了非洲人类遗传与健康联盟 (H3Africa)、其他非洲国家、牙买加和非裔美国人核心群体，开发一个由超过 50,000 名具有相关表型的参与者组成的联合资源和基因组学数据，称为非洲血统人群的心血管代谢紊乱（红衣主教）研究地点。此外，CARDINAL 研究中心将包括 5 个复制队列，规模超过 100,000 来自不同血统人群的参与者。我们的主要目标是建立 PRS 研究中心 AA 群体的方法和分析，并为其他群体协作生成和完善 PRS 通过将现有数据集与基因组学和表型数据相结合来识别不同祖先的种群一系列复杂的疾病和特征。我们的首要目标是整合表型和基因组数据集来自七项单独队列研究的约 50,000 名非洲人。随后，我们将评估 PRS 和开发一种考虑祖先特定基因组区域的新方法来改进预测以遗传亚结构为特征的人群中 PRS 的分布。最后，我们将开发一个交互式仪表板用于传播来自不同血统人群的 PRS 相关数据。 CARDINAL 研究地点非常适合对复杂疾病病因学产生新颖的生物学见解，并在全球人群中应用。 CARDINAL 团队的成员已经成功地合作了大约十年，创造并通过高影响力的出版物传播科学知识。通过在多基因风险评分多样性联盟 CARDINAL 带来了最大的非洲血统群体与会者齐聚一堂，探讨基因组学对常见 CMD 和其他非传染性疾病的贡献。