美国再生基因中心Jonathan Marchini团队宣布他们研制了基于大规模遗传研究中汇总统计数据的基因检测高效计算方法荟萃分析。相关论文于2025年11月12日发表在《自然—遗传学》杂志上。

为了应对这一挑战，研究小组提出了REMETA——一种有效的基因检测meta分析工具。REMETA为每个研究主题一个稀疏协方差参考文件，该文件为每个表型主题的单变量汇总统计数据重新缩放。该研究团队开发了病例-对照不平衡二元性状的新方法，并估计了负荷试验的等位基因频率、基因型计数和效应大小。该课题组研究人员通过对英国生物银行469376个样本的五个特征进行荟萃分析，证明了他们的方法的性能和优势。开放的REMETA软件将促进来自不同研究的大规模外显子组测序研究的荟萃分析，这些研究不容易合并。

研究人员表示，以单变量汇总统计为主题的基于基因的测试的荟萃分析是遗传关联研究的有力策略。然而，目前的方法需要在每个研究和感兴趣的性状的变体之间共享协方差矩阵。对于具有许多表型的大规模研究，这些矩阵的计算、存储和共享可能很麻烦。

附：英文原文

Title: Computationally efficient meta-analysis of gene-based tests using summary statistics in large-scale genetic studies

Author: Joseph, Tyler A., Mbatchou, Joelle, Ghosh, Arkopravo, Marcketta, Anthony, Gillies, Christopher E., Tang, Jing, Nakka, Priyanka, Zhang, Xinyuan, Kosmicki, Jack A., Sidore, Carlo, Gurski, Lauren, Ghoussaini, Maya, Ferreira, Manuel A. R., Abecasis, Gonalo, Marchini, Jonathan

Issue&Volume: 2025-11-12

Abstract: Meta-analysis of gene-based tests using single-variant summary statistics is a powerful strategy for genetic association studies. However, current approaches require sharing the covariance matrix between variants for each study and trait of interest. For large-scale studies with many phenotypes, these matrices can be cumbersome to calculate, store and share. Here, to address this challenge, we present REMETA—an efficient tool for meta-analysis of gene-based tests. REMETA uses a single sparse covariance reference file per study that is rescaled for each phenotype using single-variant summary statistics. We develop new methods for binary traits with case–control imbalance, and to estimate allele frequencies, genotype counts and effect sizes of burden tests. We demonstrate the performance and advantages of our approach through meta-analysis of five traits in 469,376 samples in UK Biobank. The open-source REMETA software will facilitate meta-analysis across large-scale exome sequencing studies from diverse studies that cannot easily be combined.

DOI: 10.1038/s41588-025-02390-0

Source: https://www.nature.com/articles/s41588-025-02390-0