The profitability of dairy activity is influenced by the genetic selection of economically important traits. In this context, the correct estimation of genetic parameters and the knowledge regarding candidate genes involved in the expression of genetically associated traits may help develop appropriate breeding strategies for the Guzerá breed. In this study, genetic parameters and candidate genes were estimated for accumulated 305-day milk yield (305MY), age at n calving (ANC), and milk yield efficiency (MYE) in Guzerá cattle. The (co)variance components were estimated by the restricted maximum likelihood method, and single nucleotide polymorphisms (SNPs) effects were estimated using the weighted single-step genome-wide association approach. The numbers of SNPs and samples used after quality control were 29,869 and 870, respectively. Candidate genes identified in a GWAS were selected to build gene networks by using the ClueGO Cytoscape plug-in (kappa score level ≥ 0.4). Heritabilities estimated for 305MY, ANC, and MYE were moderate to high (0.23, 0.41, and 0.42, respectively). Genetic correlations were positive between 305MY × ANC and 305MY × MYE (0.10 and 0.81, respectively) and negative between MYE × ANC (-0.53). Based on the GWAS analysis, a total of 89 significant SNPs (threshold value of 5.77 on the –log10 scale) were found for 305MY, and no significant SNPs were found for the other traits. Based on the top 5 significant SNPs (i.e., significant SNPs that explained the largest proportion of additive genetic variance), the following positional candidate genes were found to be related to 305MY in Guzerá cattle: CIB4, OTOF, LOXL2, PPFIA2, NXN, MRM3, GEMIN4, DBIL5, and FAM57A. In addition, the gene network analysis revealed the candidate genes BCR, P2RY12, P2RY14, GPR87, IFT81, SYT1, IL16, and HOOK3, which shared important biological processes and functions (e.g., Rho guanine nucleotide exchange factor activity, G-protein coupled purinergic nucleotide receptor signaling, intraciliary transport involved in cilium assembly, calcium ion-dependent exocytosis, chemotaxis regulation, and microtubule anchoring at centrosome), for 305MY.
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