Integrating large-scale meta-analysis of genome-wide association studies improve the genomic prediction accuracy for combined pig populations.

Abstract

The strategy of combining reference populations has been widely recognized as an effective way to enhance the accuracy of genomic prediction (GP). This study investigated the efficiency of genomic prediction using prior information and combined reference population. In total, prior information considering trait-associated single nucleotide polymorphisms (SNPs) obtained from meta-analysis of genome-wide association studies (GWAS meta-analysis) was incorporated into three models to assess the performance of GP using combined reference populations. Two different Yorkshire populations with imputed whole genome sequence (WGS) data (9,741,620 SNPs), named as P1 (1259 individuals) and P2 (1018 individuals), were used to predict genomic estimated breeding values for three live carcass traits, including backfat thickness, loin muscle area, and loin muscle depth. A 10 × 5 fold cross-validation was used to evaluate the prediction accuracy of 203 randomly selected candidate pigs from the P2 population and the reference population consisted of the remaining pigs from P2 and the stepwise added pigs from P1. By integrating SNPs with different p-value thresholds from GWAS meta-analysis downloaded from PigGTEx Project, the prediction accuracy of GBLUP, genomic feature BLUP (GFBLUP) and GBLUP given genetic architecture (BLUP|GA) were compared. Moreover, we explored effects of reference population size and heritability enrichment of genomic features on the prediction accuracy improvement of GFBLUP and BLUP|GA relative to GBLUP. The prediction accuracy of GBLUP using all WGS markers showed average improvement of 4.380% using the P1 + P2 reference population compared with the P2 reference population. Using the combined reference population, GFBLUP and BLUP|GA yielded 6.179% and 5.525% higher accuracies than GBLUP using all SNPs based on the single reference population, respectively. Positive regression coefficients were estimated in relation to the improvement in prediction accuracy (between GFBLUP/BLUP|GA and GBLUP) and the size of the reference as well as the heritability enrichment of genomic features. Compared to the classic GBLUP model, GFBLUP and BLUP|GA models integrating GWAS meta-analysis information increase the prediction accuracy and using combined populations with enlarged reference population size further enhances prediction accuracy of the two approaches. The heritability enrichment of genomic features can be used as an indicator to reflect weather prior information is accurately presented.