Standard

A genome-wide association study in 10,000 individuals links plasma N-glycome to liver disease and anti-inflammatory proteins. / Sharapov, Sodbo; Timoshchuk, Anna; Zaytseva, Olga et al.

In: Nature Communications, Vol. 16, No. 1, 5525, 01.07.2025.

Research output: Contribution to journal › Article › peer-review

Harvard

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 2025, 'A genome-wide association study in 10,000 individuals links plasma N-glycome to liver disease and anti-inflammatory proteins', Nature Communications, vol. 16, no. 1, 5525. https://doi.org/10.1038/s41467-025-60431-y

APA

Sharapov, S., Timoshchuk, A., Zaytseva, O., Maslov, D. E., Soplenkova, A., Elgaeva, E. E., Tiys, E. S., Mangino, M., Wittenbecher, C., Karssen, L., Timofeeva, M., Nostaeva, A., Vuckovic, F., Trbojević-Akmačić, I., Štambuk, T., Feoktistova, S., Potapova, N. A., Voroshilova, V., Williams, F., ... Aulchenko, Y. S. (2025). A genome-wide association study in 10,000 individuals links plasma N-glycome to liver disease and anti-inflammatory proteins. Nature Communications, 16(1), [5525]. https://doi.org/10.1038/s41467-025-60431-y

Vancouver

Sharapov S, Timoshchuk A, Zaytseva O, Maslov DE, Soplenkova A, Elgaeva EE et al. A genome-wide association study in 10,000 individuals links plasma N-glycome to liver disease and anti-inflammatory proteins. Nature Communications. 2025 Jul 1;16(1):5525. doi: 10.1038/s41467-025-60431-y

Author

Sharapov, Sodbo ; Timoshchuk, Anna ; Zaytseva, Olga et al. / A genome-wide association study in 10,000 individuals links plasma N-glycome to liver disease and anti-inflammatory proteins. In: Nature Communications. 2025 ; Vol. 16, No. 1.

BibTeX

@article{f4991fedd4464fd98688ea66f2d7226d,
title = "A genome-wide association study in 10,000 individuals links plasma N-glycome to liver disease and anti-inflammatory proteins",
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.",
author = "Sodbo Sharapov and Anna Timoshchuk and Olga Zaytseva and Maslov, {Denis e.} and Anna Soplenkova and Elgaeva, {Elizaveta e.} and Tiys, {Evgeny s.} and Massimo Mangino and Clemens Wittenbecher and Lennart Karssen and Maria Timofeeva and Arina Nostaeva and Frano Vuckovic and Irena Trbojevi{\'c}-Akma{\v c}i{\'c} and Tamara {\v S}tambuk and Sofya Feoktistova and Potapova, {Nadezhda a.} and Viktoria Voroshilova and Frances Williams and Dragan Primorac and {Van zundert}, Jan and Michel Georges and Karsten Suhre and Massimo Allegri and Nishi Chaturvedi and Malcolm Dunlop and Schulze, {Matthias b.} and Tim Spector and Tsepilov, {Yakov a.} and Gordan Lauc and Aulchenko, {Yurii s.}",
note = "The work of S.Sh., A.T., D.M., A.S., and Y.S.A. was supported by the Research Program at the Moscow State University (MSU) Institute for Artificial Intelligence. The study was conducted using the UK Biobank resource under application #59345. The work of E.E., Y.A.T. was supported by the budget project of the Institute of Cytology and Genetics FWNR-2022-0020. European Community{\textquoteright}s Seventh Framework Programme funded project PainOmics (602736). TwinsUK is funded by the Wellcome Trust, Medical Research Council, Versus Arthritis, European Union Horizon 2020, Chronic Disease Research Foundation (CDRF), Zoe Ltd and the National Institute for Health Research (NIHR) Clinical Research Network (CRN) and Biomedical Research Centre based at Guy{\textquoteright}s and St Thomas{\textquoteright} NHS Foundation Trust in partnership with King{\textquoteright}s College London. The TwinsUK Study was approved by London-Westminster Research Ethics Committee (REC reference EC04/015), and Guy{\textquoteright}s and St Thomas{\textquoteright} NHS Foundation Trust Research and Development (R&D). The TwinsUK BioBank was approved by the HRA - Liverpool East Research Ethics Committee (REC reference 19/NW/0187), IRAS ID 258513. Glycan analysis performed in Genos was supported by Horizon Europe grants GlycanSwitch (ERC Synergy grant # 101071386), INITIALIZE (grant # 101094099) and SynHealth (grant #101159018). All participants provide written, informed consent. We thank Toma Keser, Mirna {\v S}imurina, Marija Vilaj, Jerko {\v S}tambuk, Ivan Gudelj, Thomas S. Klari{\'c}, Jasminka Kri{\v s}ti{\'c}, Jelena {\v S}imunovi{\'c}, Julija Juri{\'c}, Ana Mom{\v c}ilovi{\'c}, Najda Rudman, and Maja Hani{\'c} for their assistance with glycan analysis. We thank Dmitry Shtokalo for valuable discussion and the Federal Research Center for Information and Computational Technologies SB RAS (FRC ICT SB RAS) for assistance with computational resources.",
year = "2025",
month = jul,
day = "1",
doi = "10.1038/s41467-025-60431-y",
language = "English",
volume = "16",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - A genome-wide association study in 10,000 individuals links plasma N-glycome to liver disease and anti-inflammatory proteins

AU - Sharapov, Sodbo

AU - Timoshchuk, Anna

AU - Zaytseva, Olga

AU - Maslov, Denis e.

AU - Soplenkova, Anna

AU - Elgaeva, Elizaveta e.

AU - Tiys, Evgeny s.

AU - Mangino, Massimo

AU - Wittenbecher, Clemens

AU - Karssen, Lennart

AU - Timofeeva, Maria

AU - Nostaeva, Arina

AU - Vuckovic, Frano

AU - Trbojević-Akmačić, Irena

AU - Štambuk, Tamara

AU - Feoktistova, Sofya

AU - Potapova, Nadezhda a.

AU - Voroshilova, Viktoria

AU - Williams, Frances

AU - Primorac, Dragan

AU - Van zundert, Jan

AU - Georges, Michel

AU - Suhre, Karsten

AU - Allegri, Massimo

AU - Chaturvedi, Nishi

AU - Dunlop, Malcolm

AU - Schulze, Matthias b.

AU - Spector, Tim

AU - Tsepilov, Yakov a.

AU - Lauc, Gordan

AU - Aulchenko, Yurii s.

N1 - The work of S.Sh., A.T., D.M., A.S., and Y.S.A. was supported by the Research Program at the Moscow State University (MSU) Institute for Artificial Intelligence. The study was conducted using the UK Biobank resource under application #59345. The work of E.E., Y.A.T. was supported by the budget project of the Institute of Cytology and Genetics FWNR-2022-0020. European Community’s Seventh Framework Programme funded project PainOmics (602736). TwinsUK is funded by the Wellcome Trust, Medical Research Council, Versus Arthritis, European Union Horizon 2020, Chronic Disease Research Foundation (CDRF), Zoe Ltd and the National Institute for Health Research (NIHR) Clinical Research Network (CRN) and Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London. The TwinsUK Study was approved by London-Westminster Research Ethics Committee (REC reference EC04/015), and Guy’s and St Thomas’ NHS Foundation Trust Research and Development (R&D). The TwinsUK BioBank was approved by the HRA - Liverpool East Research Ethics Committee (REC reference 19/NW/0187), IRAS ID 258513. Glycan analysis performed in Genos was supported by Horizon Europe grants GlycanSwitch (ERC Synergy grant # 101071386), INITIALIZE (grant # 101094099) and SynHealth (grant #101159018). All participants provide written, informed consent. We thank Toma Keser, Mirna Šimurina, Marija Vilaj, Jerko Štambuk, Ivan Gudelj, Thomas S. Klarić, Jasminka Krištić, Jelena Šimunović, Julija Jurić, Ana Momčilović, Najda Rudman, and Maja Hanić for their assistance with glycan analysis. We thank Dmitry Shtokalo for valuable discussion and the Federal Research Center for Information and Computational Technologies SB RAS (FRC ICT SB RAS) for assistance with computational resources.

PY - 2025/7/1

Y1 - 2025/7/1

N2 - 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.

AB - 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.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=105010101712&origin=inward

U2 - 10.1038/s41467-025-60431-y

DO - 10.1038/s41467-025-60431-y

M3 - Article

VL - 16

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 5525

ER -

ID: 68460351