| Title: | Association of creatinine level with neurodegenerative disorders: a prospective cohort study and Mendelian randomization analysis |
| Journal: | Neurological Sciences |
| Published: | 11 Jul 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40643880/ |
| DOI: | https://doi.org/10.1007/s10072-025-08361-x |
Publication 16914
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Abstract
BackgroundMultiple evidence has suggested interaction between neurodegenerative disorders (NDDs) and creatinine, a metabolite derived from the high-energy product creatine. However, findings across studies have shown inconsistency, and the effect direction remains controversial. Here, we aimed to explore the link between creatinine and the risk of NDDs.MethodsUtilizing data from the UK Biobank, we investigated the association between baseline serum and urine creatinine and the risk of common NDDs using Cox proportional hazards regression analysis. Furthermore, we performed genetic correlation and Mendelian randomization analyses based on summary statistics from genome-wide association studies.ResultsA higher level of serum creatinine at baseline was associated with a lower risk of incident amyotrophic lateral sclerosis (ALS) (beta=-0.013, SE = 0.004, P = 1.88E-03). From the genetic perspective, a significant and negative genetic correlation was identified between serum creatinine and ALS risk (genetic correlation: -0.17, P = 0.017). Mendelian randomization analysis corroborated the primary finding, indicating that serum creatinine was associated with a reduced risk of ALS (OR: 0.92, 95% CI: 0.86-0.98, P = 0.01). Moreover, a higher level of baseline serum creatinine was associated with a reduced risk of incident Alzheimer's disease (beta=-4.89E-03, SE = 2.24E-03, P = 0.03), though the effect size was small.ConclusionsThese findings enhance our understanding of creatinine's role in the risk of NDDS, suggest the potential of targeting creatinine as a biomarker of ALS, and hold implications for designing therapeutic interventions in clinical trials.</p>
3 Authors
- Peixi Wang
- Huifang Shang
- Chunyu Li
1 Application
| Application ID | Title |
|---|---|
| 98992 | Precision medicine of central nervous system diseases combining demographics, imaging, genetics, and other omics |
Enabling scientific discoveries that improve human health