Renal function and neurodegenerative diseases : a two-sample Mendelian randomization study
Renal function and neurodegenerative diseases : a two-sample Mendelian randomization study
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DOI：
10.1080/01616412.2022.2158640
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发表时间：
2023-01-20
影响因子：
1.9
通讯作者：
Tan，Lan
中科院分区：
文献类型：
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作者：
Liu，Xue;Ou，Ya-Nan;Tan，Lan
研究背景观察性研究表明肾功能与阿尔茨海默病（Alzheimer 'sdisease，AD）、帕金森病（Parkinson' sdisease，PD）、路易体痴呆（Lewybodementia，LBD）和多发性硬化（multiplesclerosis，MS）有关联。然而，目前尚不清楚这些协会是否是cause.MethodsWe使用两个样本孟德尔随机化（MR）分析，以调查肾功能和6神经退行性疾病（NDD）之间的因果关系：AD（包括家族性AD）、PD、LBD、额颞叶痴呆（FTD）、肌萎缩侧索硬化（ALS）和MS。慢性肾病（CKD）和估计的肾小球滤过率（eGFR）用于测量肾功能。逆方差加权（IVW）是主要的估计方法。结果未发现BUN、CKD、eGFR与AD、家族性AD、PD、LBD、FTD、ALS之间有任何因果关系（P均> 0. 05）。IVW分析显示eGFR与MS之间存在因果关系[比值比（OR），4.89; 95%可信区间（CI），1.43 - 16.71; P = 0.01]，但在MR-Egger和加权中位数中未得到证实（所有P值>0.05）。然而，MS与BUN无因果关系（OR，0.91; 95%CI，0.40-2.07; P = 0.82）和CKD（OR，1.04; 95%CI，0.88-1.23; P = 0.66）结论我们的研究表明eGFR降低与MS有关，本研究的价值在于，为进一步研究eGFR降低与MS之间的关系提供了方向。
BackgroundObservational 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.MethodsWe 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).ResultsThere was no indication of any causative relationship of BUN, CKD, or eGFR with AD, familial AD, PD, LBD, FTD and ALS (allPvalues >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 (allPvalues >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.ConclusionsOur 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.