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

• 批准号: 10445464
• 负责人: Bibo Jiang
• 金额: $ 81.28万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 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/10445464
• 关键词: Address; Alcohol consumption; Biology; Blood; Blood Pressure; Cause of Death; Collaborations; Complement; Complex; Data; Data Analyses; Data Set; Disease; Environmental Exposure; European; Female; Frequencies; Genetic; Genetic Heterogeneity; Genetic Models; Genetic Research; Genetic study; Heart; Heterogeneity; Human Genetics; Individual; Joints; Licensing; Linkage Disequilibrium; Lipids; Lung; 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; base; causal variant; 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

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给人类基因研究带来了革命性的变化。在过去的十年里，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 这些发现为新的生物学提供了信息，并导致了新的疗法。然而，大多数研究都集中在欧洲 样本和大多数研究都是通过将两性汇集在一起进行的。性别特异性基因 不同人群的建筑在很大程度上仍然难以捉摸。作为下一步，财团已经开始努力 汇总来自不同非欧洲人口的数据集。Meta分析经常被用于大型财团 研究迫切需要开发能够有效地进行跨世系交配的方法。 分析。为此，我们将开发一系列创新方法，以提高协会的力量 转基因分析中的作图、精细作图的精确度和多基因预测的准确性。 所产生的方法将被应用于一系列与心脏、肺和血液相关的特征，与 财团研究的数量。这是我们在统计方法开发方面的强劲记录的延续 遗传学。我们将把这些方法实现到一些广泛使用的工具中，包括RVTESTS、SEQMINER和 这不仅对我们自己的研究有益，而且对该领域的其他研究人员也有帮助。