Longitudinal Genome-Wide Association Study for Female Fertility Traits in German Holstein Cattle

The aim of this genome-wide association study (GWAS) was to detect significant SNP effects influencing the dynamic process of female fertility in dairy cattle over lactations, to identify possible candidate genes and to study their role in pathway analyses. We considered records for the female fertility traits non-return rate after 56 days (NRR56), interval from calving to first service (CTFS) and days open (DO) up to parity six from 190 269 lactating Holstein cows and heifers. The longitudinal GWAS followed a 2-step approach. In step 1, we estimated (co)variance components by combining pedigree and genomic relationships in random regression models with additive-genetic and permanent environmental regressions on the time-dependent gradient 'parity'. The matrix for estimated (co)variance components for random regression coefficients from step 1 was integrated into the longitudinal GWAS in step 2 to estimate SNP effects and significance for (a) the outer 'layer' representing baseline effects (intercept), (b) the middle 'layer' representing the slope and (c) the inner 'layer' indicating significant SNPs in all lactations, but with differing effects. For the 'inner layer', we detected the following five potential candidate genes: TMEM132C and IMPG1 for NRR56, DCHS2 for CTFS and CSMD1 and CSNK1A1 for DO. The identified genes also play a dominant role in biological pathways related to physiological fertility mechanisms. Overall, the longitudinal GWAS illustrated the dynamic genetic mechanisms of gene regulations on female fertility traits with progressing time.