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Updated: May 7, 2025

Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry
Published on: June 21, 2018
Genetic insights into therapeutic targets for gout: evidence from a multi-omics mendelian randomization study
Mingyuan Fan1, Zhangjun Yun2, Jiushu Yuan1
1Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
Background:
Considering that the treatment of gout is poor, we performed a Mendelian randomization (MR) study to identify candidate biomarkers and therapeutic targets for gout.
Methods:
A drug-targeted MR study was performed for gout by integrating the gout genome-wide association studies (GWAS) summary data and cis expression quantitative trait loci of 2,633 druggable genes from multiple cohorts. Summary data-based Mendelian randomization (SMR) analyses based on transcript and protein levels were further implemented to validate the reliability of the identified potential therapeutic targets for gout. Phenome-wide MR (Phe-MR) analysis was conducted in 1403 diseases to investigate incidental side effects of potential therapeutic targets for gout.
Results:
Eight potential therapeutic targets (ALDH3B1, FCGR2B, IL2RB, NRBP1, RCE1, SLC7A7, SUMF1, THBS3) for gout were identified in the discovery cohort using MR analysis. Replication analysis and meta-analysis implemented in the replication cohort validated the robustness of the MR findings (P < 0.05). Evidence from the SMR analysis (P < 0.05) further strengthened the reliability of the 8 potential therapeutic targets for gout also revealed that high levels of ALDH3B1 reduced the gout risk possibly modified by the methylation site cg25402137. SMR analysis (P < 0.05) at the protein level added emphasis on the impact of the risk genes NRBP1 and SUMF1 on gout. Phe-MR analysis indicated significant causality between 7 gout causal genes and 45 diseases.
Conclusion:
This study identified several biomarkers associated with gout risk, providing new insights into the etiology of gout and promising targets for the development of therapeutic agents.
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