Causal association between adiponectin and the risk of Alzheimer's disease: A Mendelian randomization study

Abstract

BackgroundNumerous observational studies have revealed that circulating adiponectin (ADPN) is associated with Alzheimer's disease (AD) risk. However, the causality remains unknown. We aimed to assess the causality of circulating ADPN on AD risk using Mendelian randomization (MR).MethodsFourteen single nucleotide polymorphisms (SNPs) significantly associated with ADPN were selected from publicly available genetic abstract data. We applied these SNPs to two recent large-scale genome-wide association studies (GWAS) of AD, one from the FinnGen consortium and the other from a large meta-analysis. The inverse variance weighted method, MR–Egger method, the weighted median method, the Cochran Q statistic, the MR-Pleiotropy Residual Sum and Outlier methods, and the leave-one-out analysis were applied for MR analyses.ResultsIn MR analysis, no significant genetic association was found between plasma ADPN levels and AD risk by analyzing the FinnGen consortium GWAS database in the inverse variance weighted method [odds ratio (OR): 0.874, 95% confidence interval (CI): 0.701–1.089, p = 0.230], MR–Egger (OR: 0.944, 95% CI: 0.692–1.288, p = 0.721), and weighted median method (OR: 0.900, 95% CI: 0.678–1.194, p = 0.449). Additionally, the same analysis was conducted for the meta-analysis database, and we found no significant association (OR: 1.000, 95% CI: 0.999–1.001, p = 0.683).ConclusionOur findings reveal no significant causal association between circulating ADPN and AD risk.

Adiponectin Gene Polymorphisms: A Case–Control Study on Their Role in Late-Onset Alzheimer’s Disease Risk

“…Based on our findings, we posit that despite the obvious effects of ADIPOQ SNPs on circulating adiponectin, this impact does not translate into a significantly increased risk of developing LOAD. This conclusion aligns with the results of a recent MR study that explored the causality between circulating adiponectin and AD risk, finding no association between genetically predicted adiponectin levels and AD [ 108 ]. The 14 SNPs used as instrumental variables in the MR analysis were selected from a 2012 GWAS meta-analysis from the ADIPOGen consortium [ 41 ] and included four variants within or in proximity to ADIPOQ .…”

The Causal Associations between Adipokines and Alzheimer’s Disease: A Two-Sample Mendelian Randomization Study

“…Our findings indicated a neuroprotective potential of adiponectin against Alzheimer's pathology. Interestingly, our findings were inconsistent with a previous MR study [30] revealing no causal effects of adiponectin on AD, using the same GWAS datasets with our study. In that study, all 14 SNPs significantly associated with adiponectin were included.…”