Genetic analysis of 249 circulating metabolic traits in 619,372 individuals from Estonian and UK Biobanks (nature.com)

• GWAS meta-analysis of 249 NMR-measured metabolic traits in 619,372 individuals from Estonian Biobank and UK Biobank.
• Identified 88,127 locus–trait associations from 8,398 loci; 19.4% of fine-mapped variants were low-frequency (MAF 0.1-1%).
• Colocalization analysis across molecular layers (eQTL, pQTL, disease GWAS) revealed 932,864 colocalization events.
• Cis-Mendelian randomization suggests that genetically lowering BCAA levels via BCKDK inhibition does not reduce T2D risk.

"A genome-wide association study meta-analysis of 249 circulating metabolic traits measured by NMR spectroscopy in up to 619,372 individuals from the Estonian Biobank and UK Biobank identified 88,127 locus–trait associations at 8,398 loci. Using fine mapping, phenome-wide colocalization, and cis-Mendelian randomization, researchers explored causal links between metabolic traits and diseases. They found that 19.4% of fine-mapped variants had minor allele frequencies between 0.1% and 1%, with twofold enrichment for missense and splice-altering variants. The study suggests that lowering branched-chain amino acid levels via BCKDK inhibition is unlikely to reduce type 2 diabetes risk."