Assessment of causality in associations between serum adiponectin and the risk of Alzheimer's disease and Parkinson's disease: A Mendelian Randomization Study

Background: Until recently, the association between circulating adiponectin (ADPN) levels and the risk of Alzheimer's disease (AD) and Parkinson's disease (PD) was unclear.Methods: We utilized public data from the IEU GWAS database for two-sample bidirectional Mendelian randomization (MR) analysis and multiple sensitivity analyses. MR analysis was performed on the aggregated data utilizing the Genetic risk score (GRS) as an instrumental variable Results: The MR analyses revealed no significant causal association between the genetically determined ADPN and AD (ORIVW = 0.852, 95% confidence interval [CI]: 0.586-1.117, P = 0.235) or PD (ORIVW = 0.830, 95% CI: 0.780-1.156, P = 0.606) risk. In the opposite direction, AD and PD also did not demonstrate any causal association with ADPN. GRS approach yielded similar results (P>0.05).But, exhibited a negative correlation with interleukin 1 (IL1, βIVW = -0.31; 95% CI: -0.55 to -0.07, P = 0.011). The Cochrane test and MR-PRESSO analysis revealed no evidence of pleiotropy in MR results.Conclusions: Our findings yielded no evidence to substantiate a causal relationship between ADPN levels and the risk of AD and PD, or vice versa. However, elevated levels of ADPN may correlate with lower levels of IL1.