C-reactive protein and risk of Alzheimer's disease.

• Higher CRP levels were significantly associated with an increased risk of AD. • The association between genetically predicted CRP levels and AD was consistent in sensitivity analysis. • No directional pleiotropy was observed in the MR-Egger regression. In this study, we examined whether C-reactive protein (CRP) play causal roles in Alzheimer's disease (AD) using Mendelian randomization (MR) analysis. Summary-level data for AD (71,880 cases and 383,378 controls) was obtained from the large meta-analyses of genome-wide association studies. As instrumental variables, we used 56 single nucleotide polymorphisms (n = 4 for conservative CRP instruments; n = 52 for liberal CRP instruments), previously identified to be associated with CRP levels (n = 194,418 and 204,402 European individuals, respectively). MR estimates were calculated using the inverse-variance weighted approach and complemented with the weighted median, MR-PRESSO, and MR-Egger methods. Genetically predicted elevated CRP levels were significantly associated with an increased risk of AD (conservative CRP instruments: odds ratio, 1.02; 95% CI, 1.01–1.04; p = 0.008). Results for liberal CRP instruments showed a consistent trend. Sensitivity analyses generated similar results and no pleiotropic bias was observed. This study indicates that genetically predicted elevated CRP levels may be a causal risk factor for AD. [ABSTRACT FROM AUTHOR]