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Cattle temperament is an interesting trait due to its correlation with production efficiency, labor safety, and animal welfare. To date, however, its genetic basis is not clearly understood. Here, we performed a genome-wide association study for a series of temperament traits in cattle, assessed with via open field and novel object tests, using autosomal single nucleotide polymorphisms (SNPs) derived from the whole-genome sequence. We identified 37 and 29 genome-wide significant loci in the open field and novel object tests, respectively. Gene set analysis revealed the most significant pathway was the neuroactive ligand-receptor interaction pathway, which may be essential for emotional control in cattle. Analysis of the expression levels of 18 tissuespecific genes based on transcriptomic data showed enrichment in the brain, with some candidate genes involved in psychiatric and neurodegenerative diseases in humans. Based on principal component analysis, the first principal component explained the largest variance in the open field and novel object test data, and the most significant loci were assigned to SORCS3 and SESTD1, respectively. Our findings should help facilitate cattle breeding for sound temperament by pyramiding favorable alleles to further improve cattle production. [ABSTRACT FROM AUTHOR]