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Causal associations between urinary sodium with body mass, shape and composition: a Mendelian randomization study.

ABSTRACT: Observational studies have found associations between urinary sodium (UNa) with obesity, body shape and composition; but the findings may be biased by residual confounding. The objective of this two-sample Mendelian randomization (MR) study was to analyze their causal associations in both sex-combined and sex-specific models. Genome-wide association studies of UNa, 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 significance level of 5?×?10-8, but further removed those SNPs with potential horizontal pleiotropy. Univariable 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 regression coefficients (beta) and their 95% confidence intervals (95% CI). The total sample size was up to 322 154. UNa was causally associated with increased BMI in both men [eGFR-adjusted beta 0.443 (0.163-0.724)] and women [0.594 (0.333-0.855)]. UNa caused BF percentage increase in men [0.622 (0.268-0.976)] and women [0.334 (0.007-0.662)]. UNa significantly elevated BMI-adjusted WHR in men [0.321 (0.094-0.548)], but not in women [0.170 (- 0.052 to 0.391)]. Additionally, we found that BMI causally increased UNa [0.043 (0.023-0.063)]. UNa 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.

SUBMITTER: Feng Q

PROVIDER: S-EPMC7562909 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Causal associations between urinary sodium with body mass, shape and composition: a Mendelian randomization study.

Feng Qi Q Yuan Shuai S Yang Qian Q Lu Yingchang Y Loos Ruth J F RJF Li Gloria H Y GHY Fei Yue Y Tsoi Man Fung MF Cheung Ching Lung CL Cheung Bernard M Y BMY

Scientific reports 20201015 1

Observational studies have found associations between urinary sodium (UNa) with obesity, body shape and composition; but the findings may be biased by residual confounding. The objective of this two-sample Mendelian randomization (MR) study was to analyze their causal associations in both sex-combined and sex-specific models. Genome-wide association studies of UNa, body mass index (BMI), BMI-adjusted waist-to-hip ratio (WHR), body fat (BF) percentage and estimated glomerular filtration rate (eGF ...[more]

PMID: 33060734

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Project description:BackgroundPsoriasis is a common inflammatory skin disease that has been reported to be associated with obesity. We aimed to investigate a possible causal relationship between body mass index (BMI) and psoriasis.Methods and findingsFollowing a review of published epidemiological evidence of the association between obesity and psoriasis, mendelian randomization (MR) was used to test for a causal relationship with BMI. We used a genetic instrument comprising 97 single-nucleotide polymorphisms (SNPs) associated with BMI as a proxy for BMI (expected to be much less confounded than measured BMI). One-sample MR was conducted using individual-level data (396,495 individuals) from the UK Biobank and the Nord-Trøndelag Health Study (HUNT), Norway. Two-sample MR was performed with summary-level data (356,926 individuals) from published BMI and psoriasis genome-wide association studies (GWASs). The one-sample and two-sample MR estimates were meta-analysed using a fixed-effect model. To test for a potential reverse causal effect, MR analysis with genetic instruments comprising variants from recent genome-wide analyses for psoriasis were used to test whether genetic risk for this skin disease has a causal effect on BMI. Published observational data showed an association of higher BMI with psoriasis. A mean difference in BMI of 1.26 kg/m2 (95% CI 1.02-1.51) between psoriasis cases and controls was observed in adults, while a 1.55 kg/m2 mean difference (95% CI 1.13-1.98) was observed in children. The observational association was confirmed in UK Biobank and HUNT data sets. Overall, a 1 kg/m2 increase in BMI was associated with 4% higher odds of psoriasis (meta-analysis odds ratio [OR] = 1.04; 95% CI 1.03-1.04; P = 1.73 × 10(-60)). MR analyses provided evidence that higher BMI causally increases the odds of psoriasis (by 9% per 1 unit increase in BMI; OR = 1.09 (1.06-1.12) per 1 kg/m2; P = 4.67 × 10(-9)). In contrast, MR estimates gave little support to a possible causal effect of psoriasis genetic risk on BMI (0.004 kg/m2 change in BMI per doubling odds of psoriasis (-0.003 to 0.011). Limitations of our study include possible misreporting of psoriasis by patients, as well as potential misdiagnosis by clinicians. In addition, there is also limited ethnic variation in the cohorts studied.ConclusionsOur study, using genetic variants as instrumental variables for BMI, provides evidence that higher BMI leads to a higher risk of psoriasis. This supports the prioritization of therapies and lifestyle interventions aimed at controlling weight for the prevention or treatment of this common skin disease. Mechanistic studies are required to improve understanding of this relationship.

Dataset Information

Causal associations between urinary sodium with body mass, shape and composition: a Mendelian randomization study.

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Causal associations between urinary sodium with body mass, shape and composition: a Mendelian randomization study.

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