Mendelian randomisation to uncover causal associations between conformation, metabolism, and production as potential exposure to reproduction in German Holstein dairy cattle

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izdano v:Genetics, Selection, Evolution vol. 57, no. 1 (Dec 2025), p. 7
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Springer Nature B.V.
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245 1 |a Mendelian randomisation to uncover causal associations between conformation, metabolism, and production as potential exposure to reproduction in German Holstein dairy cattle 
260 |b Springer Nature B.V.  |c Dec 2025 
513 |a Journal Article 
520 3 |a BackgroundReproduction is vital to welfare, health, and economics in animal husbandry and breeding. Health and reproduction are increasingly being considered because of the observed genetic correlations between reproduction, health, conformation, and performance traits in dairy cattle. Understanding the detailed genetic architecture underlying these traits would represent a major step in comprehending their interplay. Identifying known, putative or novel associations in genomics could improve animal health, welfare, and performance while allowing further adjustments in animal breeding.ResultsWe conducted genome-wide association studies for 25 different traits belonging to four different complexes, namely reproduction (n = 13), conformation (n = 6), production (n = 3), and metabolism (n = 3), using a cohort of over 235,000 dairy cows. As a result, we identified genome-wide significant signals for all the studied traits. The obtained summary statistics collected served as the input for a Mendelian randomisation approach (GSMR) to infer causal associations between putative exposure and reproduction traits. The study considered conformation, production, and metabolism as exposure and reproduction as outcome. A range of 139 to 252 genome-wide significant SNPs per combination were identified as instrumental variables (IVs). Out of 156 trait combinations, 135 demonstrated statistically significant effects, thereby enabling the identification of the responsible IVs. Combinations of traits related to metabolism (38 out of 39), conformation (68 out of 78), or production (29 out of 39) were found to have significant effects on reproduction. These relationships were partially non-linear. Moreover, a separate variance component estimation supported these findings, strongly correlating with the GSMR results and offering suggestions for improvement. Downstream analyses of selected representative traits per complex resulted in identifying and investigating potential physiological mechanisms. Notably, we identified both trait-specific SNPs and genes that appeared to influence specific traits per complex, as well as more general SNPs that were common between exposure and outcome traits.ConclusionsOur study confirms the known genetic associations between reproduction traits and the three complexes tested. It provides new insights into causality, indicating a non-linear relationship between conformation and reproduction. In addition, the downstream analyses have identified several clustered genes that may mediate this association. 
651 4 |a Germany 
653 |a Reproduction 
653 |a Genome-wide association studies 
653 |a Cattle 
653 |a Dairy cattle 
653 |a Animals 
653 |a Genes 
653 |a Animal health 
653 |a Stillbirth 
653 |a Causality 
653 |a Metabolism 
653 |a Animal breeding 
653 |a Statistical analysis 
653 |a Animal husbandry 
653 |a Ketosis 
653 |a Conformation 
653 |a Exposure 
653 |a Ovaries 
653 |a Fertility 
653 |a Milk 
653 |a Randomization 
653 |a Animal welfare 
653 |a Single-nucleotide polymorphism 
653 |a Breeding 
653 |a Environmental 
773 0 |t Genetics, Selection, Evolution  |g vol. 57, no. 1 (Dec 2025), p. 7 
786 0 |d ProQuest  |t Health & Medical Collection 
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