Sharapov Sodbo, Timoshchuk Anna, Zaytseva Olga, Maslov Denis E, Soplenkova Anna, Elgaeva Elizaveta E, Tiys Evgeny S, Mangino Massimo, Wittenbecher Clemens, Karssen Lennart, Timofeeva Maria, Nostaeva Arina, Vuckovic Frano, Trbojević-Akmačić Irena, Štambuk Tamara, Feoktistova Sofya, Potapova Nadezhda A, Voroshilova Viktoria, Williams Frances, Primorac Dragan, Van Zundert Jan, Georges Michel, Suhre Karsten, Allegri Massimo, Chaturvedi Nishi, Dunlop Malcolm, Schulze Matthias B, Spector Tim, Tsepilov Yakov A, Lauc Gordan, Aulchenko Yurii S
MSU Institute for Artificial Intelligence, Lomonosov Moscow State University, Moscow, Russia.
Genos Glycoscience Research Laboratory, Borongajska cesta 83H, Zagreb, Croatia.
Nat Commun. 2025 Jul 1;16(1):5525. doi: 10.1038/s41467-025-60431-y.
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.
超过一半的血浆蛋白是N-糖基化的。其中大多数由肝脏和淋巴组织合成、糖基化并分泌到血液中。虽然N-糖基化与越来越多的肝脏、心脏代谢和免疫疾病有关，但对这一过程的遗传调控知之甚少。在此，我们对10000名个体的血浆蛋白质组N-糖基化进行了最大规模的全基因组关联研究。通过鉴定16个新位点并对13个有助于N-糖基化的新基因进行优先级排序，我们将已知与血液N-糖基化相关的基因座数量增加了一倍。其中包括GCKR、TRIB1、HP、SERPINA1和CFH基因。这些基因主要在肝脏中表达，并显示出血浆蛋白N-糖基化、代谢和肝脏疾病以及炎症反应之间以前未知的遗传联系。通过整合糖组学、蛋白质组学、转录组学和基因组学，我们提供了一种资源，有助于更深入地探索疾病发病机制，并支持发现基于聚糖的生物标志物。
