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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.

摘要大规模的基因数据集已经彻底改变了人类基因研究。在过去的十年里，关联研究已经确定了与各种复杂性状相关的许多遗传变异。这些这些发现为新的生物学提供了信息，并导致了新的治疗方法。然而，大多数研究都集中在欧洲。大多数研究都是通过将男女样本合并在一起进行的。性别特异性遗传在不同的人群中的建筑仍然很难理解。作为下一步，财团的努力已经开始，从不同的非欧洲人口的汇总数据集。荟萃分析通常在大型联合体中使用研究迫切需要开发能够有效地进行跨祖先Meta研究的方法，分析.为此，我们将制定一系列创新方法，提高协会的权力作图、精细作图的精确性和跨祖先分析中多基因预测的准确性。所得到的方法将应用于一系列心脏，肺和血液相关的性状，与一个合作，财团研究的数量。这是我们在统计方法开发方面的良好记录的延续遗传学我们将在一些广泛使用的工具中实现这些方法，包括RVTESTS、SEQMINER和这不仅有利于我们自己的研究，也有利于该领域的其他研究人员。