Molecular quantitative trait loci in reproductive tissues impact male fertility in a large mammal

Cattle are well suited to investigate inherited variation in male fertility because insemination success is recorded in thousands of artificial insemination bulls. However, functional data from relevant tissues are lacking, which prevents fine-mapping fertility-associated genomic regions to reveal functional links between genotype and phenotype. Here, we profile testis, epididymis, and vas deferens transcriptomes in 118 mature bulls and conduct association tests between 417k molecular phenotypes and more than 21M genome-wide variants to identify 41k regulatory loci. We show that expression- and splicing-mediating variants are more than three times as frequent in testis than epididymis and vas deferens, highlighting the transcriptional complexity of testis. We identify genes (WDR19, SPATA16, KCTD19, ZDHHC1) and molecular phenotypes that are associated with male fertility through transcriptome-wide association studies and colocalization analyses, revealing molecular-genetic underpinnings of quantitative variation in male fertility. ### Competing Interest Statement The authors have declared no competing interest.