Systematic druggable genome-wide mendelian randomization identifies therapeutic targets for childhood asthma

The management and prevention of childhood asthma remain significant challenges. Mendelian randomization (MR) has emerged as a valuable tool for identifying novel therapeutic targets. In response, we conducted a comprehensive, druggable genome-wide MR analysis to elucidate potential therapeutic targets for childhood asthma. Our study integrated genomic data concerning druggable targets, expression quantitative trait loci (eQTLs), and results from genome-wide association studies on childhood asthma. Employing the MR technique, we explored the putative causal links between genes that are targets for drugs and the development of childhood asthma. To validate these causal associations, we utilized reverse MR analyses along with colocalization techniques. Moreover, we performed enrichment analysis, mapped protein interaction networks, and executed drug prediction algorithms and molecular docking studies. These methodologies were applied to gain critical insights that could guide the development of more potent and precise therapeutic agents. We identified 35 druggable genes significantly associated with childhood asthma (including BLVRA, SLC9A3, LYZ, SRPK1, HOXA5, LYVE1, S100A9, ADORA1, RPL13, IL7R, SLFN11, SHMT1, CLN8, TOP1MT, LPAR5, RNASET2, ANK1, H6PD, DSP, CDC25B, VWF, ITK, CACNG6, ITGB7, S100A8, ADAM12, ST14, BMP6, HK2, SYK, ABCA1, ULK4, KBTBD2, SLCO4C1), with BLVRA showing promise as a target. Our research suggests that BLVRA may be a promising target for childhood asthma treatment, aiding in the prioritization of drug development for childhood asthma.