Pérez-Rodríguez Paulino, de Los Campos Gustavo, Wu Hao, Vazquez Ana I, Jones Kyle
Colegio de Postgraduados, Montecillo, Estado de México 56230, México.
Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI 48824, USA.
G3 (Bethesda). 2025 Apr 17;15(4). doi: 10.1093/g3journal/jkae288.
Analyzing human genomic data from biobanks and large-scale genetic evaluations often requires fitting models with a sample size exceeding the number of DNA markers used (n>p). For instance, developing polygenic scores for humans and genomic prediction for genetic evaluations of agricultural species may require fitting models involving a few thousand SNPs using data with hundreds of thousands of samples. In such cases, computations based on sufficient statistics are more efficient than those based on individual genotype-phenotype data. Additionally, software that admits sufficient statistics as inputs can be used to analyze data from multiple sources jointly without the need to share individual genotype-phenotype data. Therefore, we developed functionality within the BGLR R-package that generates posterior samples for Bayesian shrinkage and variable selection models from sufficient statistics. In this article, we present an overview of the new methods incorporated in the BGLR R-package, demonstrate the use of the new software through simple examples, provide several computational benchmarks, and present a real-data example using data from the UK-Biobank, All of Us, and the Hispanic Community Health Study/Study of Latinos cohort demonstrating how a joint analysis from multiple cohorts can be implemented without sharing individual genotype-phenotype data, and how a combined analysis can improve the prediction accuracy of polygenic scores for Hispanics-a group severely under-represented in genome-wide association studies data.
分析生物样本库中的人类基因组数据以及进行大规模基因评估通常需要拟合样本量超过所用DNA标记数量的模型(n>p)。例如,开发人类多基因评分以及对农业物种进行基因评估的基因组预测,可能需要使用包含数十万样本的数据来拟合涉及数千个单核苷酸多态性(SNP)的模型。在这种情况下,基于充分统计量的计算比基于个体基因型-表型数据的计算更有效。此外,允许将充分统计量作为输入的软件可用于联合分析来自多个来源的数据,而无需共享个体基因型-表型数据。因此,我们在BGLR R包中开发了相关功能,可根据充分统计量为贝叶斯收缩和变量选择模型生成后验样本。在本文中,我们概述了BGLR R包中纳入的新方法,通过简单示例演示新软件的使用,提供几个计算基准,并给出一个使用来自英国生物样本库、“我们所有人”项目以及西班牙裔社区健康研究/拉丁裔研究队列数据的真实数据示例,展示了如何在不共享个体基因型-表型数据的情况下对多个队列进行联合分析,以及联合分析如何提高西班牙裔多基因评分的预测准确性——该群体在全基因组关联研究数据中代表性严重不足。