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

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， 联合研究的数量。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。

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.