Eigen decomposition expedites longitudinal genome-wide association studies for milk production traits in Chinese Holstein

Chao Ning, Dan Wang, Xianrui Zheng, Qin Zhang, Shengli Zhang, Raphael Mrode, Jian-Feng Liu

Pseudo-phenotypes, such as 305-day yields, estimated breeding values or deregressed proofs, are usually used as response variables for genome-wide association studies (GWAS) of milk production traits in dairy cattle. Computational inefficiency challenges the direct use of test-day records for longitudinal GWAS with large datasets. We propose a rapid longitudinal GWAS method that is based on a random regression model. Our method uses Eigen decomposition of the phenotypic covariance matrix to rotate the data, thereby transforming the complex mixed linear model into weighted least squares analysis. We performed a simulation study that showed that our method can control type I errors well and has higher power than a longitudinal GWAS method that does not include time-varied additive genetic effects. We also applied our method to the analysis of milk production traits in the first three parities of 6711 Chinese Holstein cows. The analysis for each trait was completed within 1 day with known variances. In total, we located 84 significant single nucleotide polymorphisms (SNPs) of which 65 were within previously reported quantitative trait loci (QTL) regions. Our rapid method can control type I errors in the analysis of longitudinal data and can be applied to other longitudinal traits. We detected QTL that were for the most part similar to those reported in a previous study in Chinese Holstein. Moreover, six additional SNPs for fat percentage and 13 SNPs for protein percentage were identified by our method. These additional 19 SNPs could be new candidate quantitative trait nucleotides for milk production traits in Chinese Holstein.