Renal function and neurodegenerative diseases : a two-sample Mendelian randomization study

ABSTRACT

Background

Observational studies showed renal function had associations with Alzheimer’s disease (AD), Parkinson’s disease (PD), Lewy body dementia (LBD) and multiple sclerosis (MS). However, it is unknown whether these associations are causal.

Methods

We use a two-sample Mendelian randomization (MR) analysis to investigate causal relationships between renal function and 6 neurodegenerative diseases (NDDs): AD (including familial AD), PD, LBD, frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS) and MS. Blood urea nitrogen (BUN), chronic kidney disease (CKD) and estimated glomerular filtration rate (eGFR) were used to measure renal function. The inverse-variance weighted (IVW) was the predominant estimation method. The results were further validated using sensitivity analysis (i.e. MR Egger regression, Cochran Q statistic of IVW, and leave-one-out method).

Results

There was no indication of any causative relationship of BUN, CKD, or eGFR with AD, familial AD, PD, LBD, FTD and ALS (all P values >0.05). The IVW analysis demonstrated a causal relationship between eGFR and MS [odds ratio (OR), 4.89; 95% confidence interval (CI), 1.43 to 16.71; P = 0.01] that was not verified in the MR-Egger and weighted median (all P values >0.05). However, no causal association of MS with BUN (OR, 0.91; 95% CI, 0.40–2.07; P = 0.82) and CKD (OR,1.04; 95% CI, 0.88–1.23; P = 0.66) was found. There was no single SNP that affects the overall trend.

Conclusions

Our study showed that reduced eGFR was related to MS. The value of this study is that it provides a direction for further research on the relationship between reduced eGFR and MS.

KEYWORDS:

• Mendelian randomization
• blood urea nitrogen
• estimated glomerular filtration rate
• neurodegenerative diseases
• chronic kidney disease

Acknowledgments

We thank Prof. Matthias Wuttke et al, Schwartzentruber et al, Marioni et al, Nalls et al, Chia R et al, Ferrari R et al, Nicolas et al, and International Multiple Sclerosis Genetics Consortium for providing the summary data on kidney function, AD, familial AD, PD, LBD, FTD, ALS and MS.

Disclosure statement

No potential conflict of interest was reported by the authors.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/01616412.2022.2158640

Additional information

Funding

This work was supported by grants from the National Natural Science Foundation of China (81971032 and 81901121)