Associations between obesity and hyperuricemia combing mendelian randomization with network pharmacology

Kailai Panlu; Zizun Zhou; Lin Huang; Lei Ge; Chengping Wen; Huiqing Lv

doi:10.1016/j.heliyon.2024.e27074

Associations between obesity and hyperuricemia combing mendelian randomization with network pharmacology

Heliyon. 2024 Mar 9;10(6):e27074. doi: 10.1016/j.heliyon.2024.e27074. eCollection 2024 Mar 30.

Authors

Kailai Panlu¹, Zizun Zhou², Lin Huang³, Lei Ge⁴, Chengping Wen³, Huiqing Lv²

Affiliations

¹ The First Clinical College of Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, China.
² School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, 311402, Hangzhou, Zhejiang, China.
³ School of Basic Medical Science, Zhejiang Chinese Medical University, 310053, Hangzhou, Zhejiang, China.
⁴ School of Civil Engineering, Chongqing Jiaotong University, Chongqing, 400074, China.

Abstract

Objective: Obesity has become a global health issue and a risk factor for hyperuricemia. However, the associations between obesity and hyperuricemia are sometimes confounding. In the present study, we performed mendelian randomization (MR) analysis to study their relationship and investigate the underlying mechanism by network pharmacology.

Method: Body mass index (BMI) and uric acid related to single nucleotide polymorphism were selected as instrumental variables for MR analysis. Three robust analytical methods are used for bidirectional MR analysis such as inverse-variance weighting, weighted median and MR-Egger regression. Then, we further performed sensitivity analysis to evaluate the horizontal pleiotropy, heterogeneities, and stability. The targets related to obesity and hyperuricemia were collected, screened and further conducted for Kyoto Encyclopedia of Genes and Genomes pathway enrichment to explore the mechanism of obesity and hyperuricemia using network pharmacology.

Results: The positive causality was indicated between BMI and hyperuricemia based on inverse variance-weighted analysis [odds ratio:1.23, 95% confidence interval: 1.11 to 1.30 for each standard deviation increase in BMI (4.6 kg/m²)]. Conversely, hyperuricemia did not influence BMI. 235 intersected targets from obesity and hyperuricemia were collected. Insulin resistance were the top 1 key target. The mechanism between obesity and hyperuricemia are associated with important pathways including adipocytokine signaling pathway, insulin resistance and cholesterol metabolism et al.

Conclusions: Our MR analysis supported the causal association between obesity and hyperuricemia based on availablegenome-wide association analysis summary statistics. Obesity leads to hyperuricemia via insulin resistance, which is a key link in the huge network pathways using network pharmacology.

Keywords: Association; Hyperuricemia; Mendelian randomization; Network pharmacology; Obesity.