Unlocking the Liver’s Health Code: Insights from 10,000 Glycan Profiles
At SynHealth, our mission is to transform healthcare from reactive “sick care” to proactive, personalised prevention. A key part of this journey is identifying the molecular signals — biological mirrors that can reveal how our lifestyle choices influence our long-term health.
Today, we highlight an important study in preventive health research titled A genome-wide association study in 10,000 individuals links plasma N-glycome to liver disease and anti-inflammatory proteins, co-authored by SynHealth project researchers from Genos Ltd, and published in Nature Communications. The paper presents insights from one of the largest comprehensive data analyses performed in the field, examining blood glycan profiles from over 10,000 individuals.
This research is particularly relevant because it moves beyond general longevity, exploring connections between these complex molecular signals and the health of a specific, critical organ: the liver.
The Science of Plasma Glycosylation and Liver Health
Identifying subtle biological changes associated with liver health remains an important challenge in preventive medicine. Traditional liver tests provide valuable information, but additional biomarkers could help detect changes that are not always captured by standard assessments.
This is where the plasma glycome offers promising opportunities. Glycans are complex sugar structures attached to proteins, influencing their function and interactions within the body. Because the liver synthesises and glycosylates many of the proteins circulating in our blood, shifts in blood glycan patterns can provide valuable insights into liver function, metabolic processes and inflammatory signalling.
Key Findings from the Study
By analysing more than 10,000 profiles, researchers have expanded our understanding of the genetic regulation of plasma glycosylation and identified variations associated with metabolic and liver disorders. Key takeaways include:
- Spotting Disease in the “Subclinical” Phase: The study doubled the number of genetic regions known to regulate plasma glycosylation. This means we can now identify individuals on a trajectory toward metabolic or liver deterioration long before physical symptoms appear or standard lab tests register a problem.
- The Blueprint of Inflammation: The research identified clear glycan states that correspond to specific pro-inflammatory and anti-inflammatory protein signatures. This confirms glycans aren’t passive bystanders; they are functional regulators of inflammatory response.
Two findings stand out:
- Early Clues to Liver Health: The study reveals important connections between plasma N-glycan patterns, liver function and metabolic disease. These findings open new possibilities for developing biomarkers that could help identify and monitor changes in liver health.
- New Insights into Inflammation: The research also highlights connections between plasma N-glycosylation and proteins involved in inflammatory processes, offering fresh perspectives on the complex relationship between glycans, metabolism and disease.
Why This Matters for SynHealth
By leveraging 15 years of pioneering Genos research on glycan biomarkers and past EU-funded initiatives, the project focuses on the valorisation of these discoveries for real-world application in Croatia and Slovenia. Through regional partnerships and technology transfer, SynHealth aims to translate research breakthroughs into clinical diagnostic tools for healthy longevity.
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Publication Information
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.
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