PSX-1 Genomic insights into reproduction traits of Nellore cattle: A meta-analysis of genomic regions

Enhancing reproductive efficiency could lead to economic benefits for Nellore producers. However, several factors limit our understanding of the main genetic factors controlling reproduction traits in Nellore cattle, including genetic differences between populations and statistical limitations. A meta-analysis can assist in pinpointing the most likely functional candidate genes, quantitative trait loci, and biological processes simultaneously associated with several traits in a group. Hence, the goal of this study was to perform a meta-analysis of genomic regions previously associated with reproduction traits in Nellore cattle, to improve our comprehension of the main genetic mechanisms regulating these traits within the breed. This study incorporated a total of 549 genomic regions sourced from 21 scientific publications, published between 2014 to 2024. The reproduction traits included in this study are scrotal circumference at various ages (365, 450, and 550 d), early pregnancy (< 31 mo of age), early puberty (defined as pregnancy at 18 mo), age at first calving, antral follicle count, calving interval, calving ease, testicular hypoplasia, stayability, heifer rebreeding, gestation length, anti-mullerian hormone concentrations, preweaning calf mortality, and post-natal mortality. All genomic regions identified in the literature were updated to the ARS-UCD1.2 genome assembly, and the Gallo R package was used to identify positional candidate genes associated with each genomic region. A total of 8,441 positional candidate genes were annotated and used in an overrepresentation analysis performed in meshr. The significant genes (adjusted P-values < 0.05) identified in the overrepresentation analysis underwent prioritization analyses using the GUILDify and ToppGene software. Subsequently, enrichment analysis of the prioritized overrepresented candidate genes was performed using the ClusterProfiler R package. The 8,441 annotated genes generated 1,757 overrepresented genes, of which 17 candidate genes were prioritized (FDR P -value ≤ 10-3). The overrepresented candidate genes that were prioritized are: SERTAD2, RFWD3, C1QTNF9B, SLFN14, CATSPERE, GFRA4, ZNF408, NOP58, ADGRG3, KIZ, REM2, FSCN3, DCAF11, ACSM4, ANKRD34B, CMKLR2-AS, and TRV-AAC1-1. The functional enrichment analysis highlighted the following genes: FSCN3 (exhibits highly specific expression in testis), CATSPERE (has a vital role in cellular processes related to reproduction and is necessary for normal