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ORIGINAL RESEARCH article

Front. Genet.
Sec. Statistical Genetics and Methodology
Volume 15 - 2024 | doi: 10.3389/fgene.2024.1426860

Mendelian Randomization Analysis Identified Potential Genes Pleiotropically Associated with Gout

Provisionally accepted
Yu Wang Yu Wang 1Jiahao Chen Jiahao Chen 2YAO HANG YAO HANG 3Yuxin Li Yuxin Li 1Xiaogang Xu Xiaogang Xu 1Delin Zhang Delin Zhang 1*
  • 1 Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi Province, China
  • 2 School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Jiangsu Province, China
  • 3 Binzhou Medical University, Yantai, China

The final, formatted version of the article will be published soon.

    This study aims to prioritize genes potentially involved in multifactorial or causal relationships with gout.Using the Summary Data-based Mendelian Randomization (SMR) approach, this research analyzed expression quantitative trait loci (eQTL) data from blood and renal tissues and genome-wide association study (GWAS) data related to gout. It sought to identify genetic loci potentially involved in gout. Heterogeneity testing was conducted with the HEIDI test, and results were adjusted for the False Discovery Rate (FDR).Blood cis-eQTL data were sourced from the eQTLGen Consortium's summary-level data, and renal tissue data came from the V8 release of the GTEx eQTL summary data.Gout GWAS data was sourced from the FinnGen Documentation of the R10 release.SMR analysis identified 14 gene probes in the eQTLGen blood summary-level data significantly associated with gout. The top five ranked genes are: ENSG00000169231 (labeled THBS3, PSMR = 4.16×10 -13 ), ENSG00000231064 (labeled THBS3-AS1, PSMR = 1.88×10 -8 ), ENSG00000163463 (labeled KRTCAP2, PSMR = 3.88×10 -6 ), ENSG00000172977 (labeled KAT5, PSMR = 1.70×10 -5 ), and ENSG00000161395 (labeled PGAP3, PSMR = 3.24×10 -5 ). Notably, increased expression of KRTCAP2 and PGAP3 is associated with an increased risk of gout, whereas increased expression of THBS3, THBS3-AS1, and KAT5 is associated with a reduced gout risk. No significant gene associations with gout were observed in renal tissue, likely due to the limited sample size of kidney tissue.Our findings have highlighted several genes potentially involved in the pathogenesis of gout. These results offer valuable insights into the mechanisms of gout and identify potential therapeutic targets for its treatment.

    Keywords: Gout, expression quantitative trait loci, Pleotropic association, summary data-based Mendelian randomization, Genome-Wide Association Study

    Received: 02 May 2024; Accepted: 22 Jul 2024.

    Copyright: © 2024 Wang, Chen, HANG, Li, Xu and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Delin Zhang, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, Jiangxi Province, China

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