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Epidemiology and Population Health

The causal role of elevated uric acid and waist circumference on the risk of metabolic syndrome components

Abstract

Background/objectives

Hyperuricemia has been found to cluster with multiple components of metabolic syndrome (MetS). It is unclear whether hyperuricemia is a downstream result of MetS or may play an upstream role in MetS development. Using the Mendelian randomization (MR) method, we examined the causal relationship between elevated uric acid and the various components of MetS with waist circumference as a positive control.

Subjects/methods

Data from 10k participants of Taiwan Biobank was used to carry out MR analysis with uric acid risk score (wGRS) and waist circumference wGRS as instrumental variables and components of MetS as the outcomes.

Results

We found that genetically increased serum uric acid corresponds to a significant increment of triglyceride (β = 0.065, p < 0.0001), systolic blood pressure (β = 1.047, p = 0.0005), diastolic blood pressure (β = 0.857, p < 0.0001), and mean arterial pressure (β = 0.920, p < 0.0001), but a significant reduction of high-density lipoprotein cholesterol (β = −0.020, p = 0.0014). Uric acid wGRS was not associated with fasting serum glucose, HbA1C, waist circumference, or BMI. On the other hand, waist circumference was causally associated with all the components of MetS including uric acid.

Conclusions

Our MR investigation shows that uric acid increment may augment the risk of MetS through increasing blood pressure and triglyceride levels and lowering HDL-C value but not through accumulating fat or hyperglycemia. High waist circumference may be a causal agent for all the components of MetS including hyperuricemia.

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Fig. 1

Data availability

The data used in this study can be applied from TWB at https://www.twbiobank.org.tw/new_web_en/index.php.

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Acknowledgements

Data analyzed in this article were collected by the TWB research project (AS-550) sponsored by Multidisciplinary Health Cloud Research Program: Technology Development and Application of Big Health Data, Academia Sinica, Taipei, Taiwan. The TWB directed by Dr. Fu-Tong Liu and Dr. Chen-Yang Shen was carried out by the Institute of Biomedical Sciences of Academia Sinica which is also responsible for data distribution. The assistance provided by the institute and all of those who contribute to the formation and data collection of the TWB is greatly appreciated. The views expressed herein are solely those of the authors.

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WHP, KMC, and MIB conceived and coordinated the investigation. MIB and KMC were responsible for the data analysis. MIB wrote the paper. WHP undertook revisions and HCY and YTH contributed intellectually to the development of this paper.

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Correspondence to Wen-Harn Pan.

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Biradar, M.I., Chiang, KM., Yang, HC. et al. The causal role of elevated uric acid and waist circumference on the risk of metabolic syndrome components. Int J Obes 44, 865–874 (2020). https://doi.org/10.1038/s41366-019-0487-9

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