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Fig. 1 | BMC Medicine

Fig. 1

From: TBK1, a prioritized drug repurposing target for amyotrophic lateral sclerosis: evidence from druggable genome Mendelian randomization and pharmacological verification in vitro

Fig. 1

Graphical abstract of genetic instrument variants selection, Mendelian randomization, identification of repurposing drugs discovery, and pharmacological analysis. A Obtaining cis-eQTL data for druggable genes by overlapping discovery cis-eQTL data and confirmatory cis-eQTL data with potentially druggable genes. The SNP data obtained through filtering for cis-eQTL data for blood and brain tissue from eQTLGen and PsychENCODE, with located within ± 100 kb of the TSS and meeting the FDR < 0.05 criteria, is considered as “Discovery cis-eQTL data”. The different sets of SNPs based on various additional selection criteria and multiple eQTL datasets are considered as “Confirmatory cis-eQTL data.” B Workflow showing the MR study and repurposing drugs discovery. Identifying druggable genes with strong genetic associations through the MR and colocalization analysis, further exploring treatment drugs associated with these druggable genes that meet the inclusion criteria. C R788 and AMX inhibit MSA-2-induced cGAS-STING signaling activation. D R788 and AMX inhibit ALS-related toxic protein mediated cGAS/STING signaling. MR Mendelian randomization, cis-eQTL cis-expression quantitative trait loci, ALS amyotrophic lateral sclerosis

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BMC Medicine

ISSN: 1741-7015

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