Genome-wide association studies pathway-based meta-analysis forresidual feed intake in beef cattle

Genome-wide association studies (GWASes) have been performed to search for genomicregions associated with residual feed intake (RFI); however inconsistent results have beenobtained. 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 enablesidentification 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 thegenetic mechanism underlying this trait. We used an efficient permutation hypothesis testthat takes into account the linkage disequilibrium patterns between SNPs and thefunctional 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 inthis pathway—methylcrotonoyl-CoA carboxylase 1(MCCC1), aldehyde oxidase 1(AOX1) andpropionyl-CoA carboxylase alpha subunit(PCCA)—were found in three different studies. Thissame pathway was also reported in a transcriptome analysis from two cattle populationsdivergently 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 combininguseful information from different studies.