Background/Aims: Interpreting genetic associations with complex traits can be greatly improved by detailed understanding of the molecular consequences of these variants. Although genome-wide association studies (GWAS) for complex diseases routinely profile 1M+ individuals, studies of molecular traits have lagged behind. We performed a GWAS meta-analysis for 249 circulating metabolic traits in the Estonian Biobank and the UK Biobank in up to 619,372 individuals. We identified 88,604 common and low25 frequency locus-metabolite associations from 8,774 independent loci that converged on shared genes and pathways. Using cis-Mendelian randomisation (MR), we explored putative causal links between metabolic traits, coronary artery disease and type 2 diabetes (T2D). We found that although plasma branched-chain amino acids (BCAAs) have been associated with T2D in observational studies, lowering BCAA levels by modulating the BCAA catabolism pathway is unlikely to reduce T2D risk. Our results provide a valuable resource for GWAS interpretation and drug target prioritisation.