Multivariate genome-wide association analysis by iterative hard thresholding.

Multivariate genome-wide association analysis by iterative hard thresholding.
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DOI:
10.1093/bioinformatics/btad193
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发表时间:
2023-04-03
期刊:
Bioinformatics (Oxford, England)
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在全基因组关联研究中,同时分析多个相关性状比逐个分析具有潜在的优势。多变量全基因组关联研究的标准方法是逐标记操作的,计算量很大。提出了一种基于迭代硬阈值的多变量全基因组关联研究的稀疏约束回归算法,并在方便的Julia包mendeliht . j1中实现。在多达100个定量特征的模拟研究中,迭代硬阈值与GEMMA的线性混合模型和mv-PLINK的典型相关分析相比,显示出相似的真阳性率,更小的假阳性率和更快的执行时间。在英国生物银行470228个变异的数据中,MendelIHT在80 GB内存占用下,在20小时内完成了三性状联合分析(),在53小时内完成了18性状联合分析()。简而言之,MendelIHT使遗传学家能够拟合一个单一的回归模型,同时考虑所有snp和数十个性状的影响。复制我们的结果的软件、文档和脚本可从https://github.com/OpenMendel/MendelIHT.jl获得。
In a genome-wide association study, analyzing multiple correlated traits simultaneously is potentially superior to analyzing the traits one by one. Standard methods for multivariate genome-wide association study operate marker-by-marker and are computationally intensive. We present a sparsity constrained regression algorithm for multivariate genome-wide association study based on iterative hard thresholding and implement it in a convenient Julia package MendelIHT.jl. In simulation studies with up to 100 quantitative traits, iterative hard thresholding exhibits similar true positive rates, smaller false positive rates, and faster execution times than GEMMA’s linear mixed models and mv-PLINK’s canonical correlation analysis. On UK Biobank data with 470 228 variants, MendelIHT completed a three-trait joint analysis () in 20 h and an 18-trait joint analysis () in 53 h with an 80 GB memory footprint. In short, MendelIHT enables geneticists to fit a single regression model that simultaneously considers the effect of all SNPs and dozens of traits. Software, documentation, and scripts to reproduce our results are available from https://github.com/OpenMendel/MendelIHT.jl.
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