Circulating metabolites associated with psoriasis in the UK Biobank and the HUNT Study: A cross-sectional study of 270,848 participants

Background Psoriasis is recognized as a systemic inflammatory disease associated with metabolic dysregulation. Understanding these metabolic changes may reveal biomarkers to elucidate disease mechanisms and predict comorbidities. While previous studies have identified psoriasis-associated metabolites, findings are often limited by sample sizes and lack validation.

We aimed to identify circulating metabolites associated with psoriasis, including cutaneous activity, severity, and psoriatic arthritis. Further, we investigated whether the metabolic signature was disease-specific compared to other immune-mediated inflammatory diseases (IMIDs).

We performed a cross-sectional analysis of 270,848 White/European individuals from the UK Biobank (n=253,924) and HUNT (n=16,924). Both cohorts used nuclear magnetic resonance spectroscopy to quantify metabolite levels, covering lipoprotein fractions and subfractions, fatty acids, and small-molecular metabolites. For each metabolite, we performed multivariable linear regression adjusting for age, sex, BMI, smoking status, and use of lipid-lowering medications.

The metabolomic profile of psoriasis was largely consistent across the two cohorts. In the model adjusted for age and sex, 116 metabolic measures were associated with psoriasis in both cohorts. After full adjustment, only Glycoprotein acetyls (GlycA) remained associated with psoriasis (coefficient [95% CI]: 0.09 [0.07-0.11] in UK Biobank and 0.11 [0.06-0.17] in HUNT). Despite more substantial metabolic alterations in cutaneous-active psoriasis, GlycA was also elevated in HUNT participants reporting no active psoriasis rash (coefficient [95% CI]: 0.12 [0.04-0.20] in non-cutaneous-active and 0.11 [0.03-0.19] in cutaneous-active psoriasis). In HUNT, severe psoriasis exhibited more pronounced metabolic alterations compared to non-severe psoriasis. Across both cohorts, phenylalanine levels were highly elevated in psoriatic arthritis compared to cutaneous psoriasis (coefficient [95% CI]: 0.41 [0.20-0.62] in UK Biobank and 0.47 [0.28-0.67] in HUNT). All IMIDs showed elevated GlycA and reduced albumin, with milder changes in atopic dermatitis. Notably, psoriasis in the HUNT cohort exhibited a distinct lipoprotein profile compared to other IMIDs.

This large-scale, cross-cohort study confirms metabolic alterations in individuals with psoriasis and highlights elevated GlycA levels regardless of cutaneous activity. The distinct metabolomic profile of psoriasis relative to other IMIDs suggests a potentially unique systemic profile. These findings offer a foundation for advancing biomarker research and mechanistic studies for psoriasis. Graphical abstractCreated in BioRender, Arham A (2026) https://BioRender.com/o3aw61n licensed under CC BY 4.0. Competing Interest Statement The authors have declared no competing interest. Funding Statement This research is funded by grants from the Liaison Committee for Education, Research and Innovation in Central Norway and the Joint Research Committee between St Olavs Hospital and the Faculty of Medicine and Health Sciences, NTNU - Norwegian University of Science and Technology. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The UK Biobank has been approved by the Northwest Multi-centre Research Ethics Committee (MREC) as a Research Tissue Bank (RTB) approval, granted in 2011 and renewed every 5 years. For more information, see: https://www.ukbiobank.ac.uk/learn-more-about-uk-biobank/about-us/ethics. The use of HUNT data has been approved by the Regional Committee for Medical and Health Research Ethics (REK), Central Norway, with application number 27420. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data availability The UK Biobank data is available to researchers for all types of health-related research that is in the public interest. Data are available for approved researchers through the UK Biobank data-access protocol. For accessing the resource, this project has been approved with application number 40135. For more information, see: https://www.ukbiobank.ac.uk/enable-your-research/apply-for-access. The HUNT data is stored in the HUNT databank (https://www.ntnu.edu/hunt/databank), and is accessible for researchers approved by the Regional Committee for Medical and Health Research Ethics. Researchers from other countries are welcome to apply in cooperation with a Norwegian Principal Investigator. For more information, see: http://www.ntnu.edu/hunt/data.