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<p>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 <i>GCKR</i>, <i>TRIB1</i>, <i>HP, SERPINA1</i> and <i>CFH</i> 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>

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A genome-wide association study in 10,000 individuals links plasma N-glycome to liver disease and anti-inflammatory proteins

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月1日

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  • 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

摘要

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.