Duarte D A S, Newbold C J, Detmann E, Silva F F, Freitas P H F, Veroneze R, Duarte M S
Department of Animal Science, Universidade Federal de Viçosa, Viçosa, 36570-000, Minas Gerais, Brazil.
Scotland's Rural College, Edinburgh, EH9 3JG, UK.
Anim Genet. 2019 Apr;50(2):150-153. doi: 10.1111/age.12761. Epub 2019 Jan 15.
Genome-wide association studies (GWASes) have been performed to search for genomic regions associated with residual feed intake (RFI); however inconsistent results have been obtained. A meta-analysis may improve these results by decreasing the false-positive rate. Additionally, pathway analysis is a powerful tool that complements GWASes, as it enables identification of gene sets involved in the same pathway that explain the studied phenotype. Because there are no reports on GWAS pathways-based meta-analyses for RFI in beef cattle, we used several GWAS results to search for significant pathways that may explain the genetic mechanism underlying this trait. We used an efficient permutation hypothesis test that takes into account the linkage disequilibrium patterns between SNPs and the functional feasibility of the identified genes over the whole genome. One significant pathway (valine, leucine and isoleucine degradation) related to RFI was found. The three genes in this pathway-methylcrotonoyl-CoA carboxylase 1 (MCCC1), aldehyde oxidase 1 (AOX1) and propionyl-CoA carboxylase alpha subunit (PCCA)-were found in three different studies. This same pathway was also reported in a transcriptome analysis from two cattle populations divergently selected for high and low RFI. We conclude that a GWAS pathway-based meta-analysis can be an appropriate method to uncover biological insights into RFI by combining useful information from different studies.
已经开展了全基因组关联研究（GWAS）来寻找与剩余采食量（RFI）相关的基因组区域；然而，得到的结果并不一致。荟萃分析可能通过降低假阳性率来改善这些结果。此外，通路分析是一种补充GWAS的有力工具，因为它能够识别参与同一通路的基因集，这些基因集可以解释所研究的表型。由于尚无关于肉牛RFI基于GWAS通路的荟萃分析的报道，我们利用多项GWAS结果来寻找可能解释该性状潜在遗传机制的显著通路。我们使用了一种有效的置换假设检验，该检验考虑了单核苷酸多态性（SNP）之间的连锁不平衡模式以及全基因组中已识别基因的功能可行性。发现了一条与RFI相关的显著通路（缬氨酸、亮氨酸和异亮氨酸降解）。该通路中的三个基因——甲基巴豆酰辅酶A羧化酶1（MCCC1）、醛氧化酶1（AOX1）和丙酰辅酶A羧化酶α亚基（PCCA）——在三项不同的研究中被发现。在对高RFI和低RFI进行不同选择的两个牛群的转录组分析中也报道了相同的通路。我们得出结论，基于GWAS通路的荟萃分析可能是一种合适的方法，通过整合来自不同研究的有用信息来揭示RFI的生物学见解。
