GWAS & Selection signatures

Dissection of genomic regions mediating correlation between complex and reproduction traits in German Holstein cattle

---

Abstract

Scrutinizing the genomic background of functional traits like reproduction and their interrelationships remains a significant challenge in dairy cattle breeding. Nowadays, large-scale datasets comprising hundreds of thousands of animals facilitate the identification of genomic regions and enable in-depth analyses of complex traits. Nevertheless, economically relevant traits often exhibit antagonistic genetic correlations with functional traits, limiting simultaneous improvement. Genetic correlations per se do not directly indicate causality, making the integration of both aspects essential to accurately characterize trait interdependencies. As correlations can differ on the global and local genomic scale and distinct forms of pleiotropy exist, specific knowledge is necessary. Finally, the detailed genomic dissection for individual traits, as well as for trait-interrelationships is prerequisite. To address this gap of local genomic differences, results from a previous Mendelian Randomisation (MR) study on reproduction traits and summary statistics from genome-wide association studies (GWAS) were used as data input for different genomic tools (ρ-HESS, SUPERGNOVA, LAVA) to estimate the local correlation and heritability (h²) based on genome partitions. Depending on the trait, between 110,629 and 192,188 cows with individual phenotypes and GWAS summary statistics were available. Further, 235,164 German Holstein cows were included for linkage disequilibrium structure to build 1,856 genome partitions on the autosomes with an average size of 1.137 mega base pair (Mbp). Reproduction traits included maternal and direct phenotypes for stillbirth and calving ease, as well as associated diseases such as metritis, retained placenta, and ovarian cycle disturbances. The impacts of production traits like milk, fat, and protein yield, as well as metabolic disorders and body condition (BCS) on reproduction traits were studied. Finally, the causal relationship between a subset of 56 trait combinations (8 exposure traits times 7 reproduction traits) was analyzed. For all traits, genome-wide significant SNPs were detected across autosomes and the X chromosome using a 50k SNP chip array, with significant global causal effects between exposure and outcome traits confirmed. This study aimed to assess two key objectives: (i) local differences for h² between causal variants, and (ii) local differences for h² or genetic correlation among pleiotropic variants. In general, the identified mediated pleiotropic variants (IVs) by MR were confirmed by the global correlation estimates. Still, trait interrelationships may arise from various forms of pleiotropy, including those that would violate MR assumptions for causality, yet still contribute to the observed trait interrelationship. Therefore, the local background for each trait and combination were analyzed separately. As example, for BCS, a region of significant local heritability on chromosome 6 (around 89 Mbp) was confirmed by the distinct tools and exhibited a positive causal effect related to reproduction. In summary, this individual local genomic background and consideration could significantly contribute to minimizing adverse interactions and enhance breeding progress.

Keywords: 2026

How to Cite:

Schwarz, L., Heise, J., Bennewitz, J., Tetens, J. & Thaller, G., (2026) “Dissection of genomic regions mediating correlation between complex and reproduction traits in German Holstein cattle”, World Congress on Genetics Applied to Livestock Production Digital Archive 2026(1): 2295613. doi: https://doi.org/10.31274/wcgalp.24349

Rights: 1