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一种用于全基因组关联研究的快速且强大的经验贝叶斯方法。

A Fast and Powerful Empirical Bayes Method for Genome-Wide Association Studies.

作者信息

Chang Tianpeng, Wei Julong, Liang Mang, An Bingxing, Wang Xiaoqiao, Zhu Bo, Xu Lingyang, Zhang Lupei, Gao Xue, Chen Yan, Li Junya, Gao Huijiang

机构信息

Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.

College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.

出版信息

Animals (Basel). 2019 May 31;9(6):305. doi: 10.3390/ani9060305.

Abstract

Linear mixed model (LMM) is an efficient method for GWAS. There are numerous forms of LMM-based GWAS methods. However, improving statistical power and computing efficiency have always been the research hotspots of the LMM-based GWAS methods. Here, we proposed a fast empirical Bayes method, which is based on linear mixed models. We call it Fast-EB-LMM in short. The novelty of this method is that it uses a modified kinship matrix accounting for individual relatedness to avoid competition between the locus of interest and its counterpart in the polygene. This property has increased statistical power. We adopted two special algorithms to ease the computational burden: Eigenvalue decomposition and Woodbury matrix identity. Simulation studies showed that Fast-EB-LMM has significantly increased statistical power of marker detection and improved computational efficiency compared with two widely used GWAS methods, EMMA and EB. Real data analyses for two carcass traits in a Chinese Simmental beef cattle population showed that the significant single-nucleotide polymorphisms (SNPs) and candidate genes identified by Fast-EB-LMM are highly consistent with results of previous studies. We therefore believe that the Fast-EB-LMM method is a reliable and efficient method for GWAS.

摘要

线性混合模型(LMM)是全基因组关联研究(GWAS)的一种有效方法。基于LMM的GWAS方法有多种形式。然而,提高统计效能和计算效率一直是基于LMM的GWAS方法的研究热点。在此,我们提出了一种基于线性混合模型的快速经验贝叶斯方法。简称为Fast-EB-LMM。该方法的新颖之处在于它使用了一种修正的亲缘关系矩阵来考虑个体间的相关性,以避免感兴趣位点与其在多基因中的对应位点之间的竞争。这一特性提高了统计效能。我们采用了两种特殊算法来减轻计算负担:特征值分解和伍德伯里矩阵恒等式。模拟研究表明,与两种广泛使用的GWAS方法EMMA和EB相比,Fast-EB-LMM显著提高了标记检测的统计效能并提高了计算效率。对中国西门塔尔肉牛群体的两个胴体性状进行的实际数据分析表明,Fast-EB-LMM鉴定出的显著单核苷酸多态性(SNP)和候选基因与先前研究结果高度一致。因此,我们认为Fast-EB-LMM方法是一种可靠且高效的GWAS方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d61c/6616871/e46171b331e2/animals-09-00305-g001.jpg

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