Identification Novel Drug Target for AD: Combined Mendelian Randomization Analysis and Bioinformation Analysis

Abstract

Background: While AD research has advanced significantly, there hasn't been a major advancement in AD therapy, in part because there aren't enough suitable therapeutic targets.

Methods: MR and transcriptome differential analysis were used to identify potential treatment targets for AD. The GEO database provided the transcriptome DEGs relevant to AD, whereas the IEU Open GWAS project provided the expression quantitative trait loci (eQTL, exposure) data. The IGAP provided the outcome data for AD. For each variant, the Wald ratio provided the estimated causal impact; for two or more genetic instruments, the inverse-variance weighted model was employed. Sensitivity analysis was performed to evaluate how reliable the MR data were. In addition, molecular docking and Enrichr analysis were used to determine the druggability of the targets.

Results: We were able to identify 1414 DGEs and perform MR analysis on them. Finally, MYBPC3 was chosen as a new AD target. There was no horizontal pleiotropy or heterogeneity found in the sensitivity analysis. Strong binding for medications and target proteins with accessible structural information was facilitated by molecular docking. 

Conclusions: According to the study, plasma MYBPC3 may be a new and promising therapeutic target for AD. It offered direction for more clinical research.

Note:
Funding Declaration: None.

Conflict of Interests: None.

Keywords: MYBPC3, Alzheimer's disease, Mendelian randomization, GWAS