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Genetic analysis of circulating metabolic traits in 619,372 individuals - PubMed

3 hours ago
  • #GWAS
  • #Metabolic Traits
  • #Genetic Analysis
  • GWAS meta-analysis of 249 circulating metabolic traits in up to 619,372 individuals from Estonian and UK Biobanks.
  • Identified 88,127 locus-trait associations from 8,398 loci, revealing shared genes and pathways.
  • Using fine mapping, phenome-wide colocalization, and cis-Mendelian randomization to explore causal links between metabolic traits and diseases.
  • Found that lowering branched-chain amino acids (BCAAs) via catabolism is unlikely to reduce type 2 diabetes risk, contrary to observational associations.
  • Low-frequency variants (0.1-1% minor allele frequency) enriched in fine-mapped variants, with a twofold increase in predicted missense and splice-altering variants.
  • Highlights the importance of integrating low-frequency variants in genetic association studies for better interpretation of variant effects.