A genome-wide association study in 10,000 individuals links plasma N-glycome to liver disease and anti-inflammatory proteins.
JSON
Sharapov S, Timoshchuk A, Zaytseva O, Maslov DE, Soplenkova A, Elgaeva EE, Tiys ES, Mangino M, Wittenbecher C, Karssen L, Timofeeva M, Nostaeva A, Vuckovic F, Trbojević-Akmačić I, Štambuk T, Feoktistova S, Potapova NA, Voroshilova V, Williams F, Primorac D, Van Zundert J, Georges M, Suhre K, Allegri M, Chaturvedi N, Dunlop M, Schulze MB, Spector T, Tsepilov YA, Lauc G, Aulchenko YS
Nat Commun 16 (1) 5525 [2025-07-01; online 2025-07-01]
More than a half of plasma proteins are N-glycosylated. Most of them are synthesized, glycosylated, and secreted to the bloodstream by liver and lymphoid tissues. While associations with N-glycosylation are implicated in the rising number of liver, cardiometabolic, and immune diseases, little is known about the genetic regulation of this process. Here, we performed the largest genome-wide association study of N-glycosylation of the blood plasma proteome in 10,000 individuals. We doubled the number of genetic loci known to be associated with blood N-glycosylation by identifying 16 novel loci and prioritizing 13 novel genes contributing to N-glycosylation. Among these were the GCKR, TRIB1, HP, SERPINA1 and CFH genes. These genes are predominantly expressed in the liver and show a previously unknown genetic link between plasma protein N-glycosylation, metabolic and liver diseases, and inflammatory response. By integrating glycomics, proteomics, transcriptomics, and genomics, we provide a resource that facilitates deeper exploration of disease pathogenesis and supports the discovery of glycan-based biomarkers.
PubMed 40593539
DOI 10.1038/s41467-025-60431-y
Crossref 10.1038/s41467-025-60431-y
pmc: PMC12218978
pii: 10.1038/s41467-025-60431-y