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基因组预测模型的全基因组关联荟萃分析。

Meta-analysis of genome-wide association from genomic prediction models.

作者信息

Bernal Rubio Y L, Gualdrón Duarte J L, Bates R O, Ernst C W, Nonneman D, Rohrer G A, King A, Shackelford S D, Wheeler T L, Cantet R J C, Steibel J P

机构信息

Departamento de Producción Animal, Facultad de Agronomía, UBA, Buenos Aires, 1417, Argentina.

Department of Animal Science, Michigan State University, East Lansing, MI, 48824-1225, USA.

出版信息

Anim Genet. 2016 Feb;47(1):36-48. doi: 10.1111/age.12378. Epub 2015 Nov 26.

Abstract

Genome-wide association (GWA) studies based on GBLUP models are a common practice in animal breeding. However, effect sizes of GWA tests are small, requiring larger sample sizes to enhance power of detection of rare variants. Because of difficulties in increasing sample size in animal populations, one alternative is to implement a meta-analysis (MA), combining information and results from independent GWA studies. Although this methodology has been used widely in human genetics, implementation in animal breeding has been limited. Thus, we present methods to implement a MA of GWA, describing the proper approach to compute weights derived from multiple genomic evaluations based on animal-centric GBLUP models. Application to real datasets shows that MA increases power of detection of associations in comparison with population-level GWA, allowing for population structure and heterogeneity of variance components across populations to be accounted for. Another advantage of MA is that it does not require access to genotype data that is required for a joint analysis. Scripts related to the implementation of this approach, which consider the strength of association as well as the sign, are distributed and thus account for heterogeneity in association phase between QTL and SNPs. Thus, MA of GWA is an attractive alternative to summarizing results from multiple genomic studies, avoiding restrictions with genotype data sharing, definition of fixed effects and different scales of measurement of evaluated traits.

摘要

基于基因组最佳线性无偏预测(GBLUP)模型的全基因组关联(GWA)研究在动物育种中很常见。然而,GWA检测的效应大小较小,需要更大的样本量来提高对稀有变异的检测能力。由于增加动物群体样本量存在困难,一种替代方法是进行荟萃分析(MA),整合来自独立GWA研究的信息和结果。尽管这种方法在人类遗传学中已被广泛使用,但在动物育种中的应用却很有限。因此,我们提出了实施GWA荟萃分析的方法,描述了基于以动物为中心的GBLUP模型计算来自多个基因组评估权重的正确方法。对真实数据集的应用表明,与群体水平的GWA相比,MA提高了关联检测能力,能够考虑群体结构和群体间方差成分的异质性。MA的另一个优点是它不需要联合分析所需的基因型数据。与这种方法实施相关的脚本,考虑了关联强度以及符号,并且进行了分发,从而考虑了数量性状位点(QTL)和单核苷酸多态性(SNP)之间关联阶段的异质性。因此,GWA的荟萃分析是汇总多个基因组研究结果的一种有吸引力的替代方法,避免了基因型数据共享、固定效应定义和评估性状测量尺度不同的限制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f90/4738412/97ea75b9631c/AGE-47-36-g001.jpg

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