Resolving Cattle GWAS Loci: Current Progress, Persistent Challenges and Future Directions

Abstract

Genome-wide association studies (GWASs) have mapped many regions affecting cattle production, health and fertility, yet the lead variant is usually a marker for a linkage-disequilibrium block rather than the molecular lesion. This state-of-the-field review examines how those loci are interpreted at different levels. The literature shows both progress and persistent limits. Colocalization may identify a likely effector transcript without establishing mediation, whereas structural variants missing from SNP-based analyses can account for expression, splicing, or complex-trait signals. Earlier reviews have audited proposed causative variants across cattle and pigs, surveyed causal variants across livestock species, or concentrated on structural variation. Here, these lines of evidence are brought together around a narrower question: Why do cattle complex-trait loci remain resolved at such different biological depths? Coding, regulatory, splicing, and structural examples show where inference is persuasive and where alternatives remain. The evidence is organized as a conceptual landscape, not a validated hierarchy or prescriptive pipeline. The available mechanistic evidence is nevertheless concentrated in commercial taurine, particularly dairy populations, which limits the direct transferability of locus-level conclusions to indicine, African taurine, composite and locally adapted cattle. Priorities include clearer causal terminology, multi-signal and multi-breed analyses, better representation of structural variation, tissue- and cell-state-matched molecular data, native bovine experimental systems and transparent reporting of unresolved explanations.