Identification and Functional Annotation of Genes Related to Horses’ Performance: From GWAS to Post-GWAS

SIMPLE SUMMARY: It is assumed that the athletic performance of horses is influenced by a large number of genes; however, to date, not many genomic studies have been performed to identify candidate genes. In this study we performed a systematic review of genome-wide association studies followed by functional analyses aiming to identify the most candidate genes for horse performance. We were successful in identifying 669 candidate genes, from which we built biological process networks. Regulatory elements (transcription factors, TFs) of these genes were identified and used to build a gene–TF network. Genes and TFs presented in this study are suggested to play a role in the studied traits through biological processes related with exercise performance, for example, positive regulation of glucose metabolism, regulation of vascular endothelial growth factor production, skeletal system development, cellular response to fatty acids and cellular response to lipids. In general, this study may provide insights into the genetic architecture underlying horse performance in different breeds around the world. ABSTRACT: Integration of genomic data with gene network analysis can be a relevant strategy for unraveling genetic mechanisms. It can be used to explore shared biological processes between genes, as well as highlighting transcription factors (TFs) related to phenotypes of interest. Unlike other species, gene–TF network analyses have not yet been well applied to horse traits. We aimed to (1) identify candidate genes associated with horse performance via systematic review, and (2) build biological processes and gene–TF networks from the identified genes aiming to highlight the most candidate genes for horse performance. Our systematic review considered peer-reviewed articles using 20 combinations of keywords. Nine articles were selected and placed into groups for functional analysis via gene networks. A total of 669 candidate genes were identified. From that, gene networks of biological processes from each group were constructed, highlighting processes associated with horse performance (e.g., regulation of systemic arterial blood pressure by vasopressin and regulation of actin polymerization and depolymerization). Transcription factors associated with candidate genes were also identified. Based on their biological processes and evidence from the literature, we identified the main TFs related to horse performance traits, which allowed us to construct a gene–TF network highlighting TFs and the most candidate genes for horse performance.