Pathway-Based Genome-Wide Association Studies for Two Meat Production Traits in Simmental Cattle.
Pathway-Based Genome-Wide Association Studies for Two Meat Production Traits in Simmental Cattle.
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基于通路的西门塔尔牛两种肉类生产性状的全基因组关联研究
DOI：
10.1038/srep18389
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发表时间：
2015-12-17
影响因子：
4.6
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Fan H;Wu Y;Zhou X;Xia J;Zhang W;Song Y;Liu F;Chen Y;Zhang L;Gao X;Gao H;Li J
全基因组关联研究（GWAS）发现的大多数单核苷酸多态性（SNP）只能解释一小部分表型变异。基于通路的GWAS被提出来提高人类某些复杂性状的基因比例，这些复杂性状可以通过丰富遗传组内的大量SNP来解释。然而，很少有人试图描述家畜的数量性状。在这项研究中，我们使用了来自807头西门塔尔牛的约7，700，000个SNP的数据集，并使用改进的基于路径的GWAS方法分析了活重和最长肌面积，以使用主成分分析（PCA）对每个基因内的高度连锁SNP进行正交化。结果，在从KEGG数据库收集的262个牛的生物学通路中，γ氨基丁酸（GABA）能突触通路和非酒精性脂肪肝病（NAFLD）通路与分析的两个性状显著相关。GABA能突触通路在生物学上适用于分析的性状，因为它在摄食量和体重增加中的作用。与最小P值和SNP集富集分析方法相比，该方法具有较高的统计功效和较低的错误发现率。
Most single nucleotide polymorphisms (SNPs) detected by genome-wide association studies (GWAS), explain only a small fraction of phenotypic variation. Pathway-based GWAS were proposed to improve the proportion of genes for some human complex traits that could be explained by enriching a mass of SNPs within genetic groups. However, few attempts have been made to describe the quantitative traits in domestic animals. In this study, we used a dataset with approximately 7,700,000 SNPs from 807 Simmental cattle and analyzed live weight and longissimus muscle area using a modified pathway-based GWAS method to orthogonalise the highly linked SNPs within each gene using principal component analysis (PCA). As a result, of the 262 biological pathways of cattle collected from the KEGG database, the gamma aminobutyric acid (GABA)ergic synapse pathway and the non-alcoholic fatty liver disease (NAFLD) pathway were significantly associated with the two traits analyzed. The GABAergic synapse pathway was biologically applicable to the traits analyzed because of its roles in feed intake and weight gain. The proposed method had high statistical power and a low false discovery rate, compared to those of the smallest P-value and SNP set enrichment analysis methods.