Functional annotation and Bayesian fine-mapping reveals candidate genes for important agronomic traits in Holstein bulls

A hundred years of data collection in dairy cattle can facilitate powerful studies of complex traits. Cattle GWAS have identified many associated genomic regions. With increasing numbers of cattle sequenced, fine-mapping of causal variants is becoming possible. Here we imputed selected sequence variants to 27,214 Holstein bulls that have highly reliable phenotypes for 35 production, reproduction, and body conformation traits. We performed single-marker scans for the 35 traits and multi-trait tests of the three trait groups, revealing 282 candidate QTL for fine-mapping. We developed a Bayesian Fine-MAPping approach (BFMAP) to integrate fine-mapping with functional enrichment analysis. Our fine-mapping identified 69 promising candidate genes, including ABCC9, VPS13B, MGST1, SCD, MKL1, CSN1S1 for production, CHEK2, GC, KALRN for reproduction, and TMTC2, ARRDC3, ZNF613, CCND2, FGF6 for conformation traits. Collectively, these results demonstrated the utility of BFMAP, identified candidate genes, and enhanced our understanding of the genetic basis of cattle complex traits.