Study Maps Genetic Links to 249 Metabolic Traits in 619,000 People

A genome-wide association study examined 249 circulating metabolic traits in up to 619,372 individuals from the Estonian Biobank and the UK Biobank. The study identified 88,127 common and low-frequency locus-trait associations from 8,398 loci. These associations converged on shared genes and pathways.

Researchers applied statistical fine mapping, phenome-wide colocalization, and cis-Mendelian randomization to explore causal connections between metabolic traits and disease outcomes. The analysis found that lowering branched-chain amino acid levels through the BCAA catabolism pathway is unlikely to reduce type 2 diabetes risk, despite prior observational associations.

1 and 1 percent. These variants showed twofold enrichment for predicted missense and splice-altering variants. The results indicate that including low-frequency variants strengthens genetic association studies of molecular traits.