Author:
Yin Zihan,Chen Jiao,Xia Manze,Zhang Xinyue,Li Yaqin,Chen Zhenghong,Bao Qiongnan,Zhong Wanqi,Yao Jin,Wu Kexin,Zhao Ling,Liang Fanrong
Abstract
AbstractNumerous 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 significant association between CCs and ANDDs. Through the genetic epidemiological approach, our study assessed the role and presented possible causal associations between CCs and ANDDs. Further studies are warranted to verify the causal associations.
Funder
National Key Research and Development Program of China
State Administration of Traditional Chinese Medicine
National Natural Science Foundation of China
the Project of Science and Technology Department of Sichuan Province
Publisher
Springer Science and Business Media LLC