Genome-Wide Association Study Based on Random Regression Model Reveals Candidate Genes Associated with Longitudinal Data in Chinese Simmental Beef Cattle

SIMPLE SUMMARY: Genome-wide association study (GWAS) has become the main approach for detecting functional genes that affects complex traits. For growth traits, the conventional GWAS method can only deal with the single-record traits observed at specific time points, rather than the longitudinal traits measured at multiple time points. Previous studies have reported the random regression model (RRM) for longitudinal data could overcome the limitation of the traditional GWAS model. Here, we present an association analysis based on RRM (GWAS-RRM) for 808 Chinese Simmental beef cattle at four stages of age. Ultimately, 37 significant single-nucleotide polymorphisms (SNPs) and several important candidate genes were screened to be associated with the body weight. Enrichment analysis showed these genes were significantly enriched in the signaling transduction pathway and lipid metabolism. This study not only offers a further understanding of the genetic basis for growth traits in beef cattle, but also provides a robust analytics tool for longitudinal traits in various species. ABSTRACT: Body weight (BW) is an important longitudinal trait that directly described the growth gain of bovine in production. However, previous genome-wide association study (GWAS) mainly focused on the single-record traits, with less attention paid to longitudinal traits. Compared with traditional GWAS models, the association studies based on the random regression model (GWAS-RRM) have better performance in the control of the false positive rate through considering time-stage effects. In this study, the BW trait data were collected from 808 Chinese Simmental beef cattle aged 0, 6, 12, and 18 months, then we performed a GWAS-RRM to fit the time-varied SNP effect. The results showed a total of 37 significant SNPs were associated with BW. Gene functional annotation and enrichment analysis indicated FGF4, ANGPT4, PLA2G4A, and ITGA5 were promising candidate genes for BW. Moreover, these genes were significantly enriched in the signaling transduction pathway and lipid metabolism. These findings will provide prior molecular information for bovine gene-based selection, as well as facilitate the extensive application of GWAS-RRM in domestic animals.