Methods to unveil sex-specific genetic architecture in trans-ancestry meta-analysis

在跨祖先荟萃分析中揭示性别特异性遗传结构的方法

基本信息

批准号：
10681351
负责人：
Bibo Jiang
金额：
$ 77.98万
依托单位：
PENNSYLVANIA STATE UNIV HERSHEY MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-10 至 2027-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10681351
关键词：
Acceleration Address Alcohol consumption Biology Blood Blood Pressure Cause of Death Collaborations Complement Complex Data Data Aggregation Data Analyses Data Set Disease Environmental Exposure European European ancestry Female Frequencies Genetic Genetic Heterogeneity Genetic Models Genetic Research Genetic study Heart Heterogeneity Human Genetics Individual Joints Licensing Linkage Disequilibrium Lipids Lung Maps Meta-Analysis Methodology Methods Modeling National Human Genome Research Institute Non-Insulin-Dependent Diabetes Mellitus Obesity Pattern Phenotype Population Population Heterogeneity Prevention strategy Privacy Research Research Personnel Resolution Resource Sharing Risk Factors Sample Size Sampling Series Sex Ratio Software Tools Strategic Planning Tobacco use Training United States National Institutes of Health Variant addiction ancestry analysis causal variant empowerment genetic architecture genetic association genetic variant genome wide association study genomic locus genotypic sex improved innovation male method development multi-ethnic novel novel therapeutics polygenic risk score public health relevance rare variant risk prediction sex statistics tool trait

项目摘要

ABSTRACT Large scale genetic datasets have revolutionized human genetic research. In the past decade, genome-wide association studies have identified numerous genetic variants associated with various complex traits. These discoveries have informed new biology and led to novel therapeutics. Yet, most studies focused on European samples and most of the studies were conducted by pooling both sexes together. Sex-specific genetic architecture in diverse populations remains largely elusive. As the next step, consortia efforts have begun to aggregate datasets from diverse non-European populations. Meta-analysis is often employed in large consortium studies There is a compelling need to develop methods that can effectively conduct trans-ancestry meta- analysis. To this end, we will develop a series of innovative methods to improve the power for association mapping, the precision of fine mapping and the accuracy of polygenic predictions in trans -ancestry analysis. Resulting methods will be applied to a series of heart, lung, and blood related traits, in collaboration with a number of consortia studies. This is a continuation of our strong track record of method development in statistical genetics. We will implement the methods into a few widely used tools, including RVTESTS, SEQMINER, and RAREMETAL, which will not only benefit our own study but also other researchers in the field.

抽象的大规模的遗传数据集彻底改变了人类遗传研究。在过去的十年中，全基因组关联研究已经确定了许多与各种复杂性状相关的遗传变异。这些发现已经了解了新的生物学，并导致了新的治疗剂。然而，大多数研究都集中在欧洲样本和大多数研究是通过将两个性别汇总在一起的。性别特异性遗传不同人口中的建筑在很大程度上难以捉摸。作为下一步，财团的努力已经开始来自不同非欧洲人群的汇总数据集。荟萃分析通常在大型财团中使用研究有迫切需要开发可以有效地进行反式元元的方法分析。为此，我们将开发一系列创新的方法来提高关联的力量映射，精细映射的精度以及在反式分析中的多基因预测的准确性。由此产生的方法将与与财团研究的数量。这是我们统计方法开发方法开发的良好记录的延续遗传学。我们将将这些方法实施到一些广泛使用的工具中，包括rvtests，seqminer和 Raremetal，这不仅会受益于我们自己的研究，而且将使该领域的其他研究人员受益。