Zhu Yahui, Li Mao, Zhang Jinghong, Huang Xusheng
Medical School of Chinese PLA, Beijing, China.
Department of Neurology, The First Medical Center, Chinese PLA General Hospital, Beijing, China.
Front Genet. 2022 May 20;13:919031. doi: 10.3389/fgene.2022.919031. eCollection 2022.
Until now, the relationship between C-reactive protein (CRP) levels and amyotrophic lateral sclerosis (ALS) risk has not been fully established. It is necessary to assess whether there is a causal relationship between C-reactive protein levels and ALS risk. We aimed to determine whether CRP has causal effects on risk of ALS. In this present study, summary-level data for ALS (20,806 cases and 59,804 controls) was obtained from large analyses of genome-wide association studies. For instrumental variables, 37 single nucleotide polymorphisms that had been previously identified to be related to CRP levels were used, including 4 SNPs of conservative CRP genetic variants and 33 SNPs of liberal CRP genetic variants. MR estimates were calculated using the inverse-variance weighted method, supplemented by MR-Egger, weighted median, and MR-PRESSO methods. There was no significant causal relationship between genetically predicted CRP levels and ALS risk (OR = 1.123, 95% CI = 0.963-1.309, = 0.139) and results for the conservative CRP instruments were consistent (OR = 0.964, 95% CI = 0.830-1.119, = 0.628). Pleiotropic bias was not observed in this study. This study suggests that genetically predicted CRP levels may not be a causal risk factor for ALS.
到目前为止，C反应蛋白（CRP）水平与肌萎缩侧索硬化症（ALS）风险之间的关系尚未完全明确。有必要评估C反应蛋白水平与ALS风险之间是否存在因果关系。我们旨在确定CRP是否对ALS风险有因果影响。在本研究中，ALS的汇总数据（20,806例病例和59,804例对照）来自全基因组关联研究的大型分析。对于工具变量，使用了先前确定与CRP水平相关的37个单核苷酸多态性，包括4个保守CRP基因变异的单核苷酸多态性和33个宽松CRP基因变异的单核苷酸多态性。采用逆方差加权法计算孟德尔随机化（MR）估计值，并辅以MR-Egger法、加权中位数法和MR-PRESSO法。基因预测的CRP水平与ALS风险之间无显著因果关系（比值比[OR]=1.123，95%置信区间[CI]=0.963-1.309，P=0.139），保守CRP工具的结果一致（OR=0.964，95%CI=0.830-1.119，P=0.628）。本研究未观察到多效性偏倚。该研究表明，基因预测的CRP水平可能不是ALS的因果风险因素。
