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Causal associations between salt intake with body mass, shape and composition: a two-sample Mendelian randomization study

By Qi Feng, Shuai Yuan, Qian Yang, Yingchang Lu, Ruth Loos, Gloria H.Y. Li, YUE FEI, Man Fung Tsoi, Ching Lung Cheung, Bernard MY Cheung

Posted 06 May 2020
medRxiv DOI: 10.1101/2020.05.01.20087007

Objective: To analyze the causal associations between salt intake with body mass, shape and composition in both sex-combined and sex-specific models. Methods: This was a two-sample Mendelian randomization study. Genome-wide association (GWA) studies of urinary sodium secretion (UNa, a surrogate for salt intake), body mass index (BMI), BMI-adjusted waist-to-hip ratio (WHR), body fat (BF) percentage and estimated glomerular filtration rate (eGFR) were identified. We initially extracted fifty SNPs associated with UNa at GWA significance level of 5 * 10(-8), but further removed those SNPs with potential horizontal pleiotropy. Univariable MR and multivariable MR with adjustment for eGFR were performed. Inverse-variance weighted MR was performed as the primary analysis, with MR-Egger methods as sensitivity analysis. The potential bidirectional association between BMI and UNa was investigated. All exposure and outcomes were continuous, and the effect measure was linear regression coefficients (beta) and their 95% confidence intervals (95%CI). Results: UNa was causally associated with increased BMI in both men (eGFR-adjusted beta 0.443 (0.163 to 0.724)) and women (0.594 (0.333 to 0.855)). UNa caused BF percentage increase in men (0.622 (0.268 to 0.976)) and women (0.334 (0.007 to 0.662)). UNa significantly elevated BMI-adjusted WHR in men (0.321 (0.094 to 0.548)), but not in women (0.170 (-0.052 to 0.391)). Additionally, we found that BMI causally increased UNa (0.043 (0.023 to 0.063)). Conclusions: Salt intake increased BMI and BF percentage. Salt intake affects male body shape by increasing BMI-adjusted WHR, but showed no effects on female body shape. The bidirectional association between BMI and UNa suggested that salt reduction measures and weight reduction measures should be implemented simultaneously to break the vicious cycle and gain more health benefits.

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