Analysis of whole genome sequencing and plasma metabolomics unveil genetic determinants and clinical implications for human health - PubMed
3 hours ago
- #metabolomics
- #biomarkers
- #genetics
- The study integrates whole-genome sequencing and plasma metabolomics data from up to 199,138 UK Biobank participants to analyze 313 metabolic biomarkers.
- It identifies 36,105 independent genetic signals, with 22.20% being novel, and 12,361 putative causal variant-trait associations, showing improved fine-mapping over array-based methods.
- Rare-variant testing reveals 1,527 protein-coding gene-trait pairs, with 32.9% unique to non-coding regions, and estimates a median heritability (h²) of 0.31, nearly triple that from array-based approaches.
- Integration with disease genetics uncovers 245 potential causal associations, such as between omega-3 fatty acids and cholelithiasis risk, and identifies 410 therapeutic targets for drug development and repurposing.
- An open-access resource (https://metabolome-whole-genome-landscape.com/) is provided to support future research on metabolic pathways, disease mechanisms, and therapeutic development.