Causal Effects of Kidney Function and Chronic Kidney Disease on Alzheimer’s Disease by Analyzing Large-Scale Genome-Wide Association Study Datasets

Abstract

Background: Alzheimer’s disease (AD) is the leading cause of dementia. Genetic components play an important role in AD and have been widely evaluated by genome-wide association studies (GWAS) and exome sequencing, and some common and rare genetic variants have been identified. In addition to genetic factors, environment factors have a role in AD. Growing evidence from observational studies linked impaired kidney function to cognitive impairment and AD; however, there are inconsistences in these findings. Objective: To determine the causal effects of impaired kidney function and chronic kidney disease (CKD) on AD. Methods: Mendelian randomization (MR) methods have been widely used to infer causal associations between exposure and outcome. Here, we conducted an MR study to investigate the causal effects of impaired kidney function and CKD on the risk of AD by analyzing large-scale GWAS datasets from FinnGen and CKD Genetics (CKDGen) Consortium. Results: We found no significant but a suggestive effect of CKD on decreased risk of AD using inverse-variance weighted (IVW) (p = 8.46E–02) and simple mode (p = 7.60E–02) methods. We identified a statistically significant effect of the estimated glomerular filtration rate (eGFR) on increased risk of AD using IVW (p = 1.11E–02), weighted median regression (p = 5.60E–03), and weighted mode (p = 2.45E–02) methods. Conclusions: Together, our findings indicate that high eGFR levels may increase the risk of AD. These findings need to be verified in future studies.