️ 91: Genome-wide Association of Plasma N-Glycome Reveals Links to Liver Disease and Anti-Inflammatory Proteins

️ Episode 91: Genome-wide Association of Plasma N-Glycome Reveals Links to Liver Disease and Anti-Inflammatory Proteins In this episode of PaperCast Base by Base, we explore a large-scale genome-wide association study that uncovers novel genetic regulators of plasma protein N-glycosylation and their connections to liver function and inflammatory pathways. Study Highlights:We conducted a meta-analysis of genome-wide association studies on 10,000 individuals from seven cohorts to identify genetic loci influencing plasma N-glycan structures. The study doubled the known glycosylation-associated loci by discovering 16 novel regions and prioritized 13 candidate genes, many of which are highly expressed in liver tissue and immune cells. Integration of glycomics, proteomics, transcriptomics, and Mendelian randomization analyses revealed genetic links between N-glycosylation, metabolic and liver diseases, and anti-inflammatory proteins such as HP, CFH, and SERPINA1. PheWAS and polygenic score analyses demonstrated pleiotropic associations between glycan-related genetic variants and complex traits including metabolic syndrome, liver disease, and immune-related conditions. Conclusion:This study provides a comprehensive resource for understanding the genetic regulation of plasma N-glycosylation and lays the groundwork for developing glycan-based biomarkers and therapeutic targets in liver and immune-related diseases. Reference: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. A genome-wide association study in 10,000 individuals links plasma N-glycome to liver disease and anti-inflammatory proteins. Nat Commun. 2025;16:5525. doi:10.1038/s41467-025-60431-y License:This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/

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