Weighted Single‐Step GWAS Reveals Genetic Mechanisms Underlying Pregnancy Loss in Early Nellore Heifers

Pregnancy loss (PL) affects reproductive efficiency in beef cattle, yet its genetic architecture remains poorly understood in Bos indicus populations. Here, PL was defined as failure from pregnancy diagnosis to calving, capturing a window approximately 60 days after the breeding season. This study aimed to identify genomic regions and biological pathways associated with PL in early Nellore heifers using weighted single-step genome-wide association study (WssGWAS). Phenotypic records from 23 507 Nellore heifers were analyzed, including 17 052 genotyped animals (GGP Indicus panel, Neogen) and 44 233 SNPs. Genomic regions explaining more than 0.5% of additive genetic variance were used to identify putative candidate genes and perform functional enrichment analysis. The estimated heritability for PL was low (0.033), indicating strong environmental influence. WssGWAS identified 25 genomic regions across 16 chromosomes, explaining 31.16% of additive genetic variance for PL. The most relevant region was located on BTA16, explaining 6.51% of the variance, although no annotated protein-coding genes were found. Additional regions occurred on BTA6, BTA14, BTA22, BTA25, and BTA29. Putative candidate genes included IL4R, IL21R, LRRC4C, RBMS3, ZFPM2, PRSS23, and NDST4, involved in immune regulation, cell adhesion, extracellular matrix remodeling, and transcriptional regulation. Functional enrichment identified Gene Ontology terms and REACTOME pathways related to nucleosome assembly, epigenetic regulation, transmembrane transport, focal adhesion, calcium signaling, immune response, and WNT signaling. These findings inform the genetic architecture of PL in Nellore cattle and suggest roles for embryo-maternal communication, immune regulation, chromatin organization, and placental development in pregnancy maintenance, supporting future functional validation and genomic selection strategies.