Circadian syndrome linked to higher Parkinson’s risk in UK Biobank cohort

In a population-based cohort study of 303,613 UK Biobank participants who were free of Parkinson’s disease at baseline, those with circadian syndrome had a 22% higher estimated risk of developing the neurological disorder than participants without the syndrome. The association persisted after adjustment for sociodemographic, lifestyle and genetic factors, with an adjusted hazard ratio of 1.22 and a 95% confidence interval of 1.11–1.34. Metabolic syndrome, by contrast, was not independently associated with Parkinson’s disease in the analysis.

Circadian syndrome, abbreviated CircS, is a cluster of conditions arising from disruption of circadian rhythms. The researchers analyzed whether this prespecified phenotype was associated with incident Parkinson’s disease during follow-up among people who had not received a Parkinson’s disease diagnosis at the start of the study. Their objectives were threefold: to assess the longitudinal association between CircS and Parkinson’s disease risk, to examine whether that association varied according to genetic susceptibility, and to determine whether CircS contained risk information beyond that captured by metabolic syndrome.

Associations were estimated using Cox proportional hazards regression, and the researchers reported hazard ratios with 95% confidence intervals. The principal result was an adjusted hazard ratio of 1.22 for participants with circadian syndrome compared with those without it, indicating a 22% higher estimated risk associated with the syndrome after the model accounted for sociodemographic, lifestyle and genetic factors. The confidence interval of 1.11–1.34 quantifies the uncertainty around that estimate. In the same adjusted analysis, metabolic syndrome showed no independent association with incident Parkinson’s disease.

The relationship between circadian-syndrome burden and Parkinson’s disease was not linear. Compared with participants without CircS, those with component scores of 5, 6 and 7 had adjusted hazard ratios of 1.51, 1.88 and 5.74, respectively. Their 95% confidence intervals were 1.21–1.88 for a score of 5, 1.36–2.61 for a score of 6 and 2.90–11.37 for a score of 7. A test of the dose-response relationship confirmed significant nonlinearity, with P for nonlinearity below 0.0001. The estimate for the highest score was therefore substantially larger than those for scores of 5 and 6, although its wide confidence interval also showed that the magnitude of the estimate was imprecise.

The study also detected an interaction between circadian syndrome and Parkinson’s disease polygenic risk score. CircS was associated with the greatest increase in Parkinson’s disease risk among participants in the low-genetic-risk group. These findings do not establish that circadian disruption causes Parkinson’s disease or that treating CircS would prevent it; as an observational cohort analysis, the study reports associations rather than causal effects. Nevertheless, the results suggest that the prespecified CircS phenotype may capture information about Parkinson’s disease risk beyond metabolic syndrome and that circadian health could become a focus for future prevention research.

Subject of Research: Association between circadian syndrome and incident Parkinson’s disease in a UK Biobank cohort

Article Title: Circadian syndrome and incident Parkinson’s disease: a population-based cohort study

Article References: Xu, X., Hou, C., Zhao, F., Lv, Y., Tan, X., & Chen, L. (2026). Circadian syndrome and incident Parkinson’s disease: a population-based cohort study. npj Parkinson's Disease. https://doi.org/10.1038/s41531-026-01545-y

Image Credits: AI Generated

DOI: 10.1038/s41531-026-01545-y

Keywords: circadian syndrome, Parkinson’s disease, UK Biobank, population cohort, incident Parkinson’s disease, polygenic risk, metabolic syndrome, circadian disruption, hazard ratio, Circadian, syndrome, incident