Associations of the circulating levels of cytokines with risk of amyotrophic lateral sclerosis: a Mendelian randomization study

BMC Medicine

Research Article

Guo-Bo Chen¹  Jie Song²  Ding Ye²  Bin Liu²  Wenkai Zhou²  Linshuoshuo Lyu²  Xiaohui Sun²  Yingying Mao² 

[1] Center for General Practice Medicine, Department of General Practice Medicine, Clinical Research Institute, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, China;Key Laboratory of Endocrine Gland Diseases of Zhejiang Province, Hangzhou, Zhejiang, China;Department of Epidemiology, Zhejiang Chinese Medical University School of Public Health, 310053, Hangzhou, China;

关键词: Amyotrophic lateral sclerosis;    Cytokine;    Genome-wide association study;    Mendelian randomization;    Single nucleotide polymorphisms;   

DOI  :  10.1186/s12916-023-02736-7

 received in 2022-05-08, accepted in 2023-01-12,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that is accompanied by muscle weakness and muscle atrophy, typically resulting in death within 3–5 years from the disease occurrence. Though the cause of ALS remains unclear, increasing evidence has suggested that inflammation is involved in the pathogenesis of ALS. Thus, we performed two-sample Mendelian randomization (MR) analyses to estimate the associations of circulating levels of cytokines and growth factors with the risk of ALS.MethodsGenetic instrumental variables for circulating cytokines and growth factors were identified from a genome-wide association study (GWAS) of 8293 European participants. Summary statistics of ALS were obtained from a GWAS including 20,806 ALS cases and 59,804 controls of European ancestry. We used the inverse-variance weighted (IVW) method as the primary analysis. To test the robustness of our results, we further performed the simple-median method, weighted-median method, MR-Egger regression, and MR pleiotropy residual sum and outlier test. Finally, a reverse MR analysis was performed to assess the possibility of reverse causation between ALS and the cytokines that we identified.ResultsAfter Bonferroni correction, genetically predicted circulating level of basic fibroblast growth factor (FGF-basic) was suggestively associated with a lower risk of ALS [odds ratio (OR): 0.74, 95% confidence interval (95% CI): 0.60–0.92, P = 0.007]. We also observed suggestive evidence that interferon gamma-induced protein 10 (IP-10) was associated with a 10% higher risk of ALS (OR: 1.10, 95% CI: 1.03–1.17, P = 0.005) in the primary study. The results of sensitivity analyses were consistent.ConclusionsOur systematic MR analyses provided suggestive evidence to support causal associations of circulating FGF-basic and IP-10 with the risk of ALS. More studies are warranted to explore how these cytokines may affect the development of ALS.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

Fig. 3