Integration of GWAS Signals and Transcriptomic Coverage Reveals Regulatory Gaps for Milk Yield and Environmental Stress Tolerance in Two Cattle Breeds

Background: This study aimed to investigate the relationship between GWAS-identified candidate regions and transcriptomic activity for milk yield and environmental stress tolerance in two cattle breeds: Holstein ( Bos taurus taurus ) and Cholistani ( Bos taurus indicus ). Candidate genomic regions related with milk yield were selected based on a meta-analysis of published GWAS findings. Differential gene expression (DGE) data were then used to assess transcriptomic coverage within these regions in both breeds. Results: It was hypothesized that candidate regions would exhibit high transcriptomic activity, given their association with functional genes. A total of 10 and 18 candidate regions were identified for milk yield and environmental stress tolerance, respectively. Contrary to expectations, transcriptomic coverage in these regions was generally low and showed no significant differences between breeds. Conclusions: These findings suggest that regulatory elements beyond the candidate genomic regions themselves may play an important role. In other words, they highlight the limitations of relying solely on GWAS signals to identify functional genomic regions underlying complex traits such as milk yield and environmental stress tolerance. Accordingly, incorporating regulatory information, such as gene regulatory network (GRN) adjacency matrices, into genomic prediction models may improve the accuracy and reliability of selection for complex traits, including milk production and resilience to environmental stress.