Sequence-based genome-wide association study and fine-mapping in German Holstein reveal new quantitative trait loci for health traits

We conducted a large GWAS of 11 health traits belonging to 3 trait complexes: (1) metabolic diseases, (2) infectious and noninfectious feet and claw disorders, and (3) udder-related traits in 100,809 to 180,217 German Holstein cows to investigate the genetic architecture and underlying biological mechanisms behind these complex traits. The GWAS identified 12,306 genome-wide significant variants across 10 traits. The new association signals were inspected with a Bayesian fine-mapping approach, leading to the discovery of 159 novel variants with high potential for causality. Variants were in known and novel regions for the traits studied, leading to a list of 53 novel candidate genes. Our study represents the largest whole-genome sequence GWAS for health traits so far, hence ensuring the power to detect meaningful variants, especially when enhanced with fine-mapping.