Simple SummaryMin pigs living in northeast China have the characteristics of good meat quality, and strong disease- and cold-resistance characters. Min pig is also one of the few pig breeds with villi hair in the world. The study of its villi hair traits is of great significance for the mechanism of cold resistance and animal welfare. In this study, a Large White × Min pigs F2 population was constructed, and a case-control genome-wide association study was performed to investigate the potential copy number variation (CNVs) associated with villi hair appearance. Finally, we found important genes related to villi. This study may also provide a basic reference for the selection and breeding of cold-resistant pigs and outdoor breeding.AbstractThe Min pig is a famous native pig breed in northeast China, which has the special genetic character of villi hair growth in cold seasons. At present, little research has focused on the genetic mechanism of villi hair growth in Min pigs. Copy number variations (CNVs) are a type of variant that may influence many traits. In this study, we first investigated the phenotype of Large White × Min pigs’ F2 pig villi hair in detail and then performed a CNV-based genome-wide association study (GWAS) between CNVs and pig villi hair appearance. Finally, a total number of 15 significant CNVRs were found to be associated with Min pig villi hair. The most significant CNVR was located on chromosome 1. Nearest gene annotation analysis indicated that the pig villi hair traits may be associated with the biological process of the G-protein-coupled receptor signaling pathway. QTL overlapping analysis found that among the CNVRs, 14 CNVRs could be co-located with known QTLs. Some genes such asMCHR2,LTBP2, andGFRA2may be candidate genes for pig villi traits and are worth further study. Our study may provide a basic reference for the selection and breeding of cold-resistant pigs and outdoor breeding.