Genetic Analysis of 249 Circulating Metabolic Traits in 619,372 Individuals Identifies 88,127 Associations (nature.com)

• Largest GWAS meta-analysis of circulating metabolic traits to date
• Identified 88,127 associations, with 19.4% of fine-mapped variants at low frequency
• Low-frequency variants twice as likely to be missense or splice-altering
• Mendelian randomization suggests BCAA lowering does not reduce T2D risk
• Novel colocalizations: plasma lactate and pulmonary embolism at GP6, GRK5, ZFPM2

"A meta-analysis of GWAS from Estonian and UK Biobanks (n=619,372) for 249 NMR-measured metabolic traits found 88,127 locus-trait associations at 8,398 loci. Fine mapping revealed 19.4% of causal variants had MAF 0.1-1%, enriched for missense and splice-altering variants. Colocalization and Mendelian randomization analyses suggest that lowering BCAA levels is unlikely to reduce type 2 diabetes risk. Novel links between plasma lactate and pulmonary embolism were identified."