Metabolomics has been integrated with genome-wide association studies and yielded insights into the genetic regulation of human metabolism. Using an updated NMR metabolomics platform, Karjalainen et al. conducted a genome-wide association meta-analysis of 233 metabolic traits in up to 136,016 participants from 33 cohorts, across multiple ancestry groups including non-Finnish European, Finnish, South Asian, East Asian, and African. This largely increased sample size led to the identification of around 8,000 genetic associations of circulating metabolic biomarkers involving more than 400 independent loci. The metabolic traits included lipid and lipoprotein parameters and non-lipid traits. Ancestry-stratified comparisons showed that the associations were broadly transferable across ancestries. Further analyses of metabolic associations revealed clusters of genes with similar metabolic profiles, suggesting the potential role of TRIM5 in mediating lipid and lipoprotein levels and therefore cardiovascular diseases. Metabolic trait-associated variants were found to be associated with risk of diseases such as intrahepatic cholestasis of pregnancy. Mendelian randomization suggested a causal association between acetone levels and hypertension. The study offers a rich dataset that might hopefully facilitate further research on human metabolism and health.

Original reference: Nature https://doi.org/10.1038/s41586-024-07148-y (2024)