| Title: | A genome-wide association study in 10,000 individuals links plasma N-glycome to liver disease and anti-inflammatory proteins |
| Journal: | Nature Communications |
| Published: | 1 Jul 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40593539/ |
| DOI: | https://doi.org/10.1038/s41467-025-60431-y |
| URL: | https://www.nature.com/articles/s41467-025-60431-y.pdf |
Publication 16354
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Abstract
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.</p>
17 Keywords
- Biomarkers
- Blood Proteins
- Female
- Genome-Wide Association Study
- Glycomics
- Glycosylation
- Haptoglobins
- Humans
- Intracellular Signaling Peptides and Proteins
- Liver
- Liver Diseases
- Male
- Polymorphism, Single Nucleotide
- Polysaccharides
- Proteome
- Proteomics
- alpha 1-Antitrypsin
31 Authors
- Sodbo Sharapov
- Anna Timoshchuk
- Olga Zaytseva
- Denis E. Maslov
- Anna Soplenkova
- Elizaveta E. Elgaeva
- Evgeny S. Tiys
- Massimo Mangino
- Clemens Wittenbecher
- Lennart Karssen
- Maria Timofeeva
- Arina Nostaeva
- Frano Vuckovic
- Irena Trbojević-Akmačić
- Tamara Štambuk
- Sofya Feoktistova
- Nadezhda A. Potapova
- Viktoria Voroshilova
- Frances Williams
- Dragan Primorac
- Jan Van Zundert
- Michel Georges
- Karsten Suhre
- Massimo Allegri
- Nishi Chaturvedi
- Malcolm Dunlop
- Matthias B. Schulze
- Tim Spector
- Yakov A. Tsepilov
- Gordan Lauc
- Yurii S. Aulchenko
1 Application
| Application ID | Title |
|---|---|
| 59345 | The impact of rare genetic variants on cardiovascular diseases and their risk factors |
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