Genetic regulation of circulating metabolome in cattle

The circulating metabolome serves as a crucial intermediary between genetics and complex traits, but conventional genome-wide studies, even in humans, often overlook dynamic physiological states or cellular regulatory processes. In this study, researchers introduce the Cattle Metabolome Atlas, an extensive database containing 3,436 plasma metabolites and 4,851 serum metabolites from 4,651 cattle.

These samples were collected from animals at various parity and lactation stages, along with their corresponding sequence-level genotypes. The investigation uncovered 728 plasma and 622 serum metabolite quantitative trait loci (mQTL), which display varying regulatory patterns depending on the context. By combining these mQTL with multi-tissue expression quantitative trait loci (eQTL) and a single-cell atlas of 59 tissues, the study found that 74-79% of mQTLs overlap with eQTLs in 29 tissues, emphasizing the liver as a central hub for systemic metabolic regulation.

Additionally, the researchers mapped 538 gene-tissue-metabolite-trait cascades associated with 11 complex traits in cattle. Cross-species analyses revealed partial evolutionary conservation between cattle and humans, underscoring the value of this atlas for cattle genetics, breeding, and comparative biology research.