满血复活。注意:这个blupf90的新功能,貌似有点问题,好几个人测试显示SSGWAS结果P-value不显示。还未坐实,待我测试后公布。
小编寄语
一直以来,GWAS和GS一直是分家的,各搞各的,交叉很少。两者都是基于统计分析,GWAS重点在于找到显著性的SNP位点,找到关联性状的基因。GS的重点在于计算个体的育种值,进行排名选择。
基因组选择基于BLUP的方法(GBLUP,SSGBLUP)省略了SNP效应的估算,直接计算育种值(BLUP),随着基因组选择在育种中广泛的实施,GS和GWAS的结合变得更有意义:
blupf90
软件在2014年就提出了SSGWAS,但是只能计算SNP的效应值,没有办法计算SNP的P-value,下面这篇文章介绍他们的团队对软件进行了升级,使得preGSf90
模块可以计算SNP的P-value。这样,就可以在动物育种中使用了,特别是有大量系谱信息和一部分基因型信息以及大量表型信息的育种群体,基于GS和SSGWAS的MAS在特定群体的选择更具前景!
https://gsejournal.biomedcentral.com/track/pdf/10.1186/s12711-019-0469-3
在这里插入图片描述
背景
一步法(SSGBLUP)在基因组育种中广泛应用,SSGWAS在此框架下一直没有显著性检验,我们的目的在于开发SSGWAS的显著性检验(p-value),并且在实际数据中进行了测试。
Single-step genomic best linear unbiased prediction (SSGBLUP) is a comprehensive method for genomic prediction. Point estimates of marker efects from SSGBLUP are often used for genome-wide association studies (GWAS) without a formal framework of hypothesis testing. Our objective was to implement p-values for singlemarker GWAS studies within the single-step GWAS (SSGWAS) framework by deriving computational algorithms and procedures, and by applying these to a large beef cattle population
方法
P-values were obtained based on the prediction error (co)variances for single nucleotide polymorphisms (SNPs), which were obtained from the prediction error (co)variances of genomic predictions based on the inverse of the coefcient matrix and formulas to estimate SNP efects.
结果
Computation of p-values took a negligible time for a dataset with almost 2 million animals in the pedigree and 1424 genotyped sires, and no infation of statistics was observed. The SNPs that passed the Bonferroni threshold of 10−5.9 were the same as those that explained the highest proportion of additive genetic variance, but even at the same signifcance levels and efects, some of them explained less genetic variance due to lower allele frequency
结论
The use of a p-value for SSGWAS is a very general and efcient strategy to identify quantitative trait loci (QTL). It can be used for complex datasets such as those used in animal breeding, where only a proportion of the pedigreed animals are genotyped.
EMMAX框架:
SSGWAS框架:
第一步:构建H矩阵
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第二步:构建混合线性方程组
第三步:计算系数矩阵稀疏逆矩阵
第四步:求解方程组
第五步:计算育种值
第六步:计算SNP效应值
第七步:计算标准误
第八步:计算SNP的P-value
使用blupf90
家族中的preGSf90
程序,计算p-value时使用的参数是OPTION snp_p_value
。软件下载:
http://nce.ads.uga.edu/html/projects/programs/Linux/64bit/