This study sheds light on the genetic complexity and interplay of production, body size, and metabolic health in dairy cattle. Phenotypes for body size-related traits from conformation classification (130,166 animals) and production (101,562 animals) of primiparous German Holstein cows were available. Additionally, 21,992, 16,641, and 7,096 animals were from herds with recordings of the metabolic diseases ketosis, displaced abomasum, and milk fever in first, second, and third lactation. Moreover, all animals were genotyped. Heritabilities of traits and genetic correlations between all traits were estimated and GWAS were performed. Heritability was between 0.240 and 0.333 for production and between 0.149 and 0.368 for body size traits. Metabolic diseases were lowly heritable, with estimates ranging from 0.011 to 0.029 in primiparous cows, from 0.008 to 0.031 in second lactation, and from 0.037 to 0.052 in third lactation. Production was found to have negative genetic correlations with body condition score (BCS; -0.279 to -0.343) and udder depth (-0.348 to -0.419). Positive correlations were observed for production and body depth (0.138-0.228), dairy character (DCH) (0.334-0.422), and stature (STAT) (0.084-0.158). In first parity cows, metabolic disease traits were unfavorably correlated with production, with genetic correlations varying from 0.111 to 0.224, implying that higher yielding cows have more metabolic problems. Genetic correlations of disease traits in second and third lactation with production in primiparous cows were low to moderate and in most cases unfavorable. While BCS was negatively correlated with metabolic diseases (-0.255 to -0.470), positive correlations were found between disease traits and DCH (0.269-0.469) as well as STAT (0.172-0.242). Thus, the results indicate that larger and sharper animals with low BCS are more susceptible to metabolic disorders. Genome-wide association studies revealed several significantly associated SNPs for production and conformation traits, confirming previous findings from literature. Moreover, for production and conformation traits, shared significant signals on Bos taurus autosome (BTA) 5 (88.36 Mb) and BTA 6 (86.40 to 87.27 Mb) were found, implying pleiotropy. Additionally, significant SNPs were observed for metabolic diseases on BTA 3, 10, 14, 17, and 26 in first lactation and on BTA 2, 6, 8, 17, and 23 in third lactation. Overall, this study provides important insights into the genetic basis and interrelations of relevant traits in today's Holstein cattle breeding programs, and findings may help to improve selection decisions.
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