权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Evolution of genetic disease risks over time and space

遗传病风险随时间和空间的演变

基本信息

批准号：
10673157
负责人：
Joseph L. Lachance
金额：
$ 37.61万
依托单位：
GEORGIA INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-05 至 2024-07-31
项目状态：
已结题

项目摘要

Project summary This research project bridges the gap between evolutionary genetics and genetic epidemiology. In the past few years, a large number of genome-wide association studies have identified thousands of disease susceptibility loci. However, the vast majority of these studies have focused on individuals with European ancestry. Many disease loci have yet to be discovered, and disease-associations that are presently known suffer from ascertainment bias. A major public health challenge is to accurately predict hereditary disease risks in other populations. Previous work has revealed that hereditary disease risks have evolved over human history and that disease risks are correlated with different genetic ancestries. This proposed research plan combines multiple approaches: analysis of ancient and modern genomes, mathematical modeling, and bioinformatics tool development. It examines the evolutionary causes of differences in genetic disease risks across populations, and it will help extend precision medicine to individuals who have diverse ancestries. By applying genomic medicine approaches to ancient DNA, this project will be result in a better understanding of how health and disease have evolved in the recent past. Mathematical models and computer simulations will be used to generate testable predictions about what sorts of genetic architectures contribute the most to health inequities. This project includes development of a novel ancestry painting approach that will improve predictions of hereditary disease risks for individuals whose genomes contain a mix of different ancestries. This project also involves generating improved genetic risk scores that correct for ascertainment bias and evolutionary history while incorporating details of molecular cell biology. The effectiveness of this approach will be assessed using phenotypic data from multiple populations. A major goal of this project is to understand how disease risks have come to vary across the globe, and this work will help extend the benefits of genomic medicine to individuals who have diverse ancestries.

项目摘要这项研究项目弥合了进化遗传学和遗传学之间的差距。流行病学在过去的几年里，大量的全基因组关联研究已经确定了数千种疾病易感基因座。但绝这些研究中的大多数都集中在具有欧洲血统的个体上。许多疾病位点尚未被发现，而目前已知遭受确认偏差。公共卫生的一个主要挑战是准确预测其他人群的遗传性疾病风险。先前的工作已经揭示了遗传性疾病的风险在人类历史上不断演变，疾病风险与不同的遗传祖先相关。这项拟议的研究该计划结合了多种方法：分析古代和现代基因组，数学建模和生物信息学工具开发。会审查不同人群遗传疾病风险差异的进化原因，将有助于将精准医疗扩展到具有不同祖先的个体。通过将基因组医学方法应用于古代DNA，该项目将导致更好地了解健康和疾病在最近的过去是如何演变的。数学模型和计算机模拟将用于生成可测试的预测哪种遗传结构对健康最有贡献不平等这个项目包括一个新的祖先绘画方法的发展这将改善对遗传性疾病风险的预测，基因组包含不同祖先的混合体。该项目还涉及生成改善遗传风险评分，纠正确定偏差和进化同时结合分子细胞生物学的细节。的有效性将使用来自多个群体的表型数据来评估该方法。一该项目的主要目标是了解疾病风险如何变化这项工作将有助于将基因组医学的益处扩展到拥有不同祖先的人。