Causal associations of obesity with chronic kidney disease and arterial stiffness: a Mendelian randomization study,The Journal of Clinical Endocrinology & Metabolism

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Causal associations of obesity with chronic kidney disease and arterial stiffness: a Mendelian randomization study
The Journal of Clinical Endocrinology & Metabolism ( IF 5.8 ) Pub Date : 2021-08-27 , DOI: 10.1210/clinem/dgab633
Chaojie Ye _{1,

2} , Lijie Kong _{1,

2} , Zhiyun Zhao _{1,

2} , Mian Li _{1,

2} , Shuangyuan Wang _{1,

2} , Hong Lin _{1,

2} , Yu Xu _{1,

2} , Jieli Lu _{1,

2} , Yuhong Chen _{1,

2} , Yiping Xu ₃ , Weiqing Wang _{1,

2} , Guang Ning _{1,

2} , Yufang Bi _{1,

2} , Min Xu _{1,

2} , Tiange Wang _{1,

2}

Affiliation

Abstract

Purpose

Observational studies have associated obesity with chronic kidney disease (CKD) and arterial stiffness, but the causality remains unclear. We aimed to investigate the causality of obesity with CKD and arterial stiffness using Mendelian randomization (MR) analysis.

Methods

We genotyped 14 body mass index (BMI)-associated variants validated in East Asians in 11384 Chinese adults. A genetic risk score based on the 14 variants and the 14 individual single nucleotide polymorphisms were respectively used as instrumental variables (IVs). CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m ². Arterial stiffness was defined as brachial-ankle pulse wave velocity >1550 cm/s.

Results

Using the genetic risk score as the IV, we demonstrated causal relations of each 1-standard deviation increment in BMI with CKD (odds ratio [OR]: 2.36; 95% confidence interval [CI]: 1.11-5.00) and arterial stiffness (OR: 1.71; 95% CI: 1.22-2.39). Using the 14 single nucleotide polymorphisms individually as IVs, each 1-standard deviation increment in BMI casually associated with CKD (OR: 2.58; 95% CI: 1.39-4.79) and arterial stiffness (OR: 1.87; 95% CI: 1.24-2.81) in the inverse-variance weighted analysis, and MR-Egger regression revealed no evidence of horizontal pleiotropy (Both P for intercept≥0.34). The causality between obesity and CKD was validated in two-sample MR analysis among Europeans (681275 of Genetic Investigation of ANthropometric Traits and 133413 of CKD Genetics).

Conclusions

This study provided novel insights into causality of obesity with CKD and arterial stiffness, highlighting the importance of weight management for primary prevention and control of subclinical vascular diseases.

更新日期：2021-08-29

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