ArticleArchives of Iranian medicine2025
Potential Therapeutic Targets for Neuroblastoma Screened through Mendelian Randomization Analysis.
Article in Archives of Iranian medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundNeuroblastoma (NB) is the most prevalent extracranial solid tumor in children. Therefore, urgent exploration of novel therapeutic targets and more effective approaches is imperative to enhance the prognosis of these children.
methodsNB datasets were obtained from OpenGWAS-ieu-a-816 (1,627 cases; 3,254 controls; European ancestry) and prot-a-2003 (N=3,301; European ancestry)-and were combined by inverse-variance meta-analysis. Adrenal expression quantitative trait loci (eQTL) data were sourced from GTEx v8 (n=233). Bidirectional Mendelian randomization (MR) and summary-based MR analyses were conducted to infer the causal relationship between adrenal-related genes and NB, with validation by Steiger directionality testing and phenotype scanning. Blood cis-eQTL datasets were obtained from eQTLGen (n=31,684 across 37 cohorts), and immune-cell data were retrieved from OpenGWAS (731 traits; IDs ebi-a-GCST90001391-GCST90002121). Using immune-cell traits as intermediate variables, bidirectional MR assessed the causal relationship between blood-related genes and NB, and colocalization analysis was performed for blood-related genes and immune cells.
resultsUsing two-sample bidirectional MR, we identified eight adrenal genes associated with NB risk. Upregulated expression of CPNE1 (OR 0.94, 95% CI [0.93-0.95];
conclusionThis study revealed that certain genes in the adrenal glands and blood affect the occurrence of NB, with immune cells playing a crucial role in the process influenced by blood genes. MR and colocalization prioritize candidate genes/putative therapeutic targets for NB.
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