Data Sheet 1_Assessment of causality association between serum adiponectin levels and the risk of Alzheimer’s disease and Parkinson’s disease: a Mendelian randomization study.docx

BackgroundUntil recently, the association between circulating adiponectin (ADPN) levels and the risk of Alzheimer’s disease (AD) and Parkinson’s disease (PD) remained unclear.
MethodsWe utilized public data from the IEU GWAS database to conduct a two-sample bidirectional Mendelian randomization (MR) analysis and multiple sensitivity analyses. The MR analysis was performed using the aggregated data, with the genetic risk score (GRS) serving as an instrumental variable.
ResultsThe MR analyses revealed no significant causal association between genetically determined ADPN levels and the risk of 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). Conversely, neither AD nor PD demonstrated any causal association with ADPN levels. The GRS approach yielded similar results (p > 0.05). However, it exhibited a negative correlation with interleukin 1β (IL1β, βIVW = −0.31; 95% CI: −0.55 to −0.07, p = 0.011). The Cochrane’s Q test and MR-PRESSO analysis revealed no evidence of pleiotropy.
ConclusionOur findings provide 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 IL1β.

背景 直至近期，循环脂联素（adiponectin, ADPN）水平与阿尔茨海默病（Alzheimer’s disease, AD）、帕金森病（Parkinson’s disease, PD）的发病风险之间的关联仍不明确。
方法 本研究利用IEU全基因组关联研究（Genome-Wide Association Study, GWAS）数据库的公开数据，开展两样本双向孟德尔随机化（Mendelian randomization, MR）分析及多项敏感性分析。本研究使用汇总数据开展MR分析，以遗传风险评分（genetic risk score, GRS）作为工具变量。
结果 孟德尔随机化分析显示，由遗传因素决定的脂联素水平与阿尔茨海默病发病风险（逆方差加权法比值比ORIVW=0.852，95%置信区间[CI]：0.586–1.117，p=0.235）、帕金森病发病风险（ORIVW=0.830，95%置信区间[CI]：0.780–1.156，p=0.606）均无显著因果关联。反之，阿尔茨海默病与帕金森病亦未显示出与脂联素水平存在任何因果关联。采用遗传风险评分方法得到了相似的结果（p>0.05）。然而，脂联素水平与白细胞介素1β（interleukin 1β, IL1β）呈负相关（βIVW=-0.31；95%置信区间[CI]：-0.55–-0.07，p=0.011）。科克伦Q检验（Cochrane’s Q test）与MR-PRESSO分析均未发现多效性证据。
结论 本研究结果未发现脂联素水平与阿尔茨海默病、帕金森病发病风险之间存在因果关联，反之亦然。然而，脂联素水平升高可能与白细胞介素1β水平降低相关。