Nanoparticle enriched mass spectrometry proteomics in British South Asians identifies novel variant-protein-disease mechanisms

In this large-scale proteogenomic study, researchers applied a nanoparticle-enabled plasma proteomics workflow (Seer Proteograph^® XT) to deeply profile blood from more than 1,400 British-Bangladeshi and British-Pakistani individuals — an ancestrally diverse population not well represented in prior pQTL studies.

Across ~8,000 quantified protein groups integrated with exome and common-variant data, the team identified over 1,200 significant variant–protein associations, including 895 cis-pQTLs, about half of which are newly reported. The MS-based proteomics data also revealed many signals not detected by SomaLogic or Olink assays run on the same samples, highlighting its complementary biological coverage. By combining proteogenomic findings with external genetic and expression evidence, the study implicated 21 proteins across 44 diseases, including a notable link between elevated IGLV3-21 levels and Graves’ disease.

These results demonstrate how deep, untargeted proteomics in diverse cohorts can uncover novel regulatory mechanisms and disease-relevant biology, expanding biomarker and drug-target discovery beyond the reach of affinity-only approaches.