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Nanoparticle-enriched mass spectrometry proteomics in British South Asians identifies links between genetic variants, plasma protein levels and disease risk
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DOI：10.1038/s41588-026-02697-6.png)
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Abstract
En 中文
Understanding genetic variation associated with differences in plasma protein levels can elucidate human disease mechanisms. Here we demonstrate how untargeted nanoparticle-enriched mass spectrometry (MS)-based plasma proteomics delivers quantitatively and qualitatively different insights compared to two affinity-based assays in a sample of ~1,400 British South Asian individuals. We identify >1,200 significant locus–protein associations (P < 8.7 × 10−12; n = 895 cis-protein quantitative trait loci (pQTLs)), more than half of which have not been reported previously. Cross-platform comparison demonstrated that multiple platforms are required to capture the full spectrum of pQTLs of blood proteins. We combine proteogenomic results with evidence from multiple biological domains to suggest a potential role of 21 proteins in the pathology of 44 diseases, including a previously uncharacterized role of immunoglobulin λ variable 3-21 in the development of Graves’ disease. Our results demonstrate the potential of MS-based blood proteomics in non-European ancestries for pQTL discovery and the need to consolidate proteogenomic evidence to confidently assign proteins to disease pathology. This study reports genetic effects on mass spectrophotometry-based plasma proteomics in a cohort of ~1,400 British South Asians, accessing parts of the proteome missed by other proteomics platforms. The resulting protein quantitative trait loci are integrated with genome-wide association study data to find potential mechanisms of disease.
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