Genome-Wide Association Studies (GWAS) help identify polymorphic sites or genes linked to phenotypic variance, but a few genes / SNPs are unlikely to explain the phenotypic variability of complex traits. In the study, the focus was moved from single loci to functional units, expressed by the metabolic pathways (KEGG). Consequently, this study aimed to estimate KEGG effects on stature in three Nordic dairy cattle breeds using SNPs effects from GWAS as the dependent variable. The SNPs were annotated to genes, then the genes to KEGG pathways.
The effects of KEGG were estimated separately for each breed using a mixed linear model incorporating the similarity between pathways expressed by common genes. The analysis yielded two conclusions: a single gene in a pathway's component may have a large impact on the pathway's overall effect or the high pathway effect may be due to the influence of many genes constituting the pathway.