Mendelian randomization analysis: The causal relationship between C-reactive protein and amyloidosis and between C-reactive protein and atherosclerosis

孟德尔随机化分析:C反应蛋白与淀粉样变性以及C反应蛋白与动脉粥样硬化之间的因果关系

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Abstract

BACKGROUND: A number of studies have shown that elevated CRP is linked to AS and reduced CRP is linked to amyloidosis. However, the exact mechanism explaining this connection is not known. METHODS: We used genomic pooled data from the Genome-Wide Association Study (GWAS) in a two-sample, two-way Mendelian randomization (MR) analysis study. Methods used included inverse variance weighting (IVW), weighted median (WM), MR-Egger method, Cochran's Q, MR-PRESSO, MR-Egger intercept test, and leave-one-out sensitivity analysis. To investigate the specific causal relationship between C-reactive protein and amyloidosis and between C-reactive protein and atherosclerosis (coronary, cerebral, aortic, and peripheral atherosclerosis). The study procedure was performed with the STROBE-MR checklist. RESULTS: There was a inverse association between C-reactive protein and amyloidosis and an positive causal relationship between C-reactive protein and aortic atherosclerosis. The development of aortic atherosclerosis was positively correlated with C-reactive protein levels (IVW:p = 0.003, OR=1.203,95% CI:1.066-1.358). Whereas amyloidosis onset was associated with reduced C-reactive protein levels (IVW:p = 0.022, OR=0.582,95% CI:0.366-0.924). Reverse Mendelian randomization analysis found no evidence of reverse causality. CONCLUSION: We verified the existence of a negative association between C-reactive protein and amyloidosis and a positive association between C-reactive protein and atherosclerosis by Mendelian randomization, which may provide some reference value for subsequent studies and treatment in the clinic.

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