Assessing causal relationship between circulating cytokines and age-related neurodegenerative diseases: a bidirectional two-sample Mendelian randomization analysis

作者：Zihan Yin, Jiao Chen, Manze Xia, Xinyue Zhang, Yaqin Li, Zhenghong Chen, Qiong-Nan Bao, Wanqi Zhong, Jin Yao, Kexin Wu, Ling Zhao, Fanrong Liang · 发表于：Scientific Reports · 年份：2023 · DOI：10.1038/s41598-023-39520-9 · 被引用次数：14 · 研究领域：GDF15 and Related Biomarkers、Bioinformatics and Genomic Networks、Nuclear Receptors and Signaling

Numerous studies have reported that circulating cytokines (CCs) are linked to age-related neurodegenerative diseases (ANDDs); however, there is a lack of systematic investigation for the causal association. A two-sample bidirectional Mendelian Randomisation (MR) method was utilized to evaluate the causal effect. We applied genetic variants correlated with concentrations of CCs from a genome-wide association study meta-analysis (n = 8293) as instrumental variables. Summary data of three major ANDDs [Alzheimer's disease (AD), Parkinson's disease (PD), and Amyotrophic lateral sclerosis (ALS)] were identified from the IEU OpenGWAS platform (n = 627, 266). Inverse-variance weighted method is the main approach to analyse causal effect, and MR results are verified by several sensitivity and pleiotropy analyses. In directional MR, it suggested that several CCs were nominally correlated with the risk of ANDDs, with a causal odds ratio (OR) of Interleukin (IL)-5 of 0.909 for AD; OR of IL-2 of 1.169 for PD; and OR of Beta nerve growth factor of 1.142 for ALS). In reverse MR, there were some suggestively causal effects of ANDDs on CCs (AD on increased Basic fibroblast growth factor and IL-12 and decreased Stem cell growth factor beta; PD on decreased Monokine induced by interferon-gamma; ALS on decreased Basic fibroblast growth factor and IL-17). The findings were stable across sensitivity and pleiotropy analyses. However, after Bonferroni correction, there is no statistically significan...