1. Systematic Druggable Genome‐Wide Mendelian Randomization Identifies Therapeutic Targets for Functional Outcome After Ischemic Stroke
- Author
-
Lu‐Yang Zhang, Yun‐Hui Chu, Yun‐Fan You, Ming‐Hao Dong, Xiao‐Wei Pang, Lian Chen, Li‐Fang Zhu, Sheng Yang, Luo‐Qi Zhou, Ke Shang, Gang Deng, Jun Xiao, Wei Wang, Chuan Qin, and Dai‐Shi Tian
- Subjects
drug target ,functional outcome ,genetics ,Mendelian randomization ,stroke ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background Stroke is a leading cause of death worldwide, with a lack of effective treatments for improving the prognosis. The aim of the present study was to identify novel therapeutic targets for functional outcome after ischemic stroke . Methods and Results Cis‐expression quantitative trait loci data for druggable genes were used as instrumental variables. The primary outcome was the modified Rankin Scale score at 3 months after ischemic stroke, evaluated as a dichotomous variable (3–6 versus 0–2) and also as an ordinal variable. Drug target Mendelian randomization, Steiger filtering analysis, and colocalization analysis were performed. Additionally, phenome‐wide Mendelian randomization analysis was performed to identify the safety of the drug target genes at the genetic level. Among >2600 druggable genes, genetically predicted expression of 16 genes (ABCC2, ATRAID, BLK, CD93, CHST13, NR1H3, NRBP1, PI3, RIPK4, SEMG1, SLC22A4, SLC22A5, SLCO3A1, TEK, TLR4, and WNT10B) demonstrated the causal associations with ordinal modified Rankin Scale (P
- Published
- 2024
- Full Text
- View/download PDF