Sequence-based GWAS meta-analyses for beef production traits.

Background: Combining the results of within-population genome-wide association studies (GWAS) based on whole-genome sequences into a single meta-analysis (MA) is an accurate and powerful method for identifying variants associated with complex traits. As part of the H2020 BovReg project, we performed sequence-level MA for beef production traits. Five partners from France, Switzerland, Germany, and Canada contributed summary statistics from sequence-based GWAS conducted with 54,782 animals from 15 purebred or crossbred populations. We combined the summary statistics for four growth, nine morphology, and 15 carcass traits into 16 MA, using both fixed effects and z-score methods.

Results: The fixed-effects method was generally more informative to provide indication on potentially causal variants, although we combined substantially different traits in each MA. In comparison with within-population GWAS, this approach highlighted (i) a larger number of quantitative trait loci (QTL), (ii) QTL more frequently located in genomic regions known for their effects on growth and meat/carcass traits, (iii) a smaller number of genomic variants within the QTL, and (iv) candidate variants that were more frequently located in genes. MA pinpointed variants in genes, including MSTN, LCORL, and PLAG1 that have been previously associated with morphology and carcass traits. We also identified dozens of other variants located in genes associated with growth and carcass traits, or with a function that may be related to meat production (e.g., HS6ST1, HERC2, WDR75, COL3A1, SLIT2, MED28, and ANKAR). Some of these variants overlapped with expression or splicing QTL reported in the cattle Genotype-Tissue Expression atlas (CattleGTEx) and could therefore regulate gene expression.

Conclusions: By identifying candidate genes and potential causal variants associated with beef production traits in cattle, MA demonstrates great potential for investigating the biological mechanisms underlying these traits. As a complement to within-population GWAS, this approach can provide deeper insights into the genetic architecture of complex traits in beef cattle.