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PubMed · 40162558

A Causal Effect of Serum 25(OH)D Level on Appendicular Muscle Mass: Evidence From NHANES Data and Mendelian Randomization Analyses.

Qian Ren·Jinrong Liang·Yanmei Su·Ruijing Tian·Junxian Wu·Sheng Ge·Peizhan Chen
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Abstract

BACKGROUND: Low serum vitamin D status was reported to be associated with reduced muscle mass; however, it is inconclusive whether this relationship is causal. This study used data from the National Health and Nutrition Examination Survey (NHANES) and two-sample Mendelian randomization (MR) analyses to ascertain the causal relationship between serum 25-hydroxyvitamin D [25(OH)D] and appendicular muscle mass (AMM). METHODS: In the NHANES 2011-2018 dataset, 11&#x2009;242 participants (5588 males and 5654 females) aged 18-59&#x2009;years old were included, and multivariant linear regression was performed to assess the relationship between 25(OH)D and AMM measured by dual-energy X-ray absorptiometry. In two-sample MR analysis, 167 single nucleotide polymorphisms significantly associated with serum 25(OH)D at the genome-wide association level (p&#x2009;<&#x2009;5&#x2009;&#xd7;&#x2009;10-8) were applied as instrumental variables (IVs) to assess vitamin D effects on AMM in the UK Biobank (417&#x2009;580 Europeans) using univariable and multivariable MR (MVMR) models. RESULTS: In the NHANES dataset, serum 25(OH)D concentrations were positively associated with AMM (&#x3b2;&#x2009;=&#x2009;0.013, SE&#x2009;=&#x2009;0.001, p&#x2009;<&#x2009;0.001) in all participants, after adjustment for age, race, season of blood collection, education, income, body mass index and physical activity. In stratification analysis by sex, males (&#x3b2;&#x2009;=&#x2009;0.024, SE&#x2009;=&#x2009;0.002, p&#x2009;<&#x2009;0.001) showed more pronounced positive associations than females (&#x3b2;&#x2009;=&#x2009;0.003, SE&#x2009;=&#x2009;0.002, p&#x2009;=&#x2009;0.024). In univariable MR, genetically higher serum 25(OH)D levels were positively associated with AMM in all participants (&#x3b2;&#x2009;=&#x2009;0.049, SE&#x2009;=&#x2009;0.024, p&#x2009;=&#x2009;0.039) and males (&#x3b2;&#x2009;=&#x2009;0.057, SE&#x2009;=&#x2009;0.025, p&#x2009;=&#x2009;0.021), but only marginally significant in females (&#x3b2;&#x2009;=&#x2009;0.043, SE&#x2009;=&#x2009;0.025, p&#x2009;=&#x2009;0.090) based on IVW models was noticed. No significant pleiotropy effects were detected for the IVs in the two-sample MR investigations. In MVMR analysis, a positive causal effect of 25(OH)D on AMM was observed in the total population (&#x3b2;&#x2009;=&#x2009;0.116, SE&#x2009;=&#x2009;0.051, p&#x2009;=&#x2009;0.022), males (&#x3b2;&#x2009;=&#x2009;0.111, SE&#x2009;=&#x2009;0.053, p&#x2009;=&#x2009;0.036) and females (&#x3b2;&#x2009;=&#x2009;0.124, SE&#x2009;=&#x2009;0.054, p&#x2009;=&#x2009;0.021). CONCLUSIONS: Our results suggested a positive causal effect of serum 25(OH)D concentration on AMM; however, more researches are warranted to unveil the underlying biological mechanisms and evaluate the effects of vitamin D intervention on AMM.

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HumansMendelian Randomization AnalysisMaleVitamin DFemaleNutrition SurveysAdultMiddle AgedAdolescentYoung AdultMuscle, SkeletalPolymorphism, Single Nucleotide25&#x2010;hydroxyvitamin DMendelian randomizationNHANESappendicular muscle masssingle nucleotide polymorphismJournal ArticleResearch Support, Non-U.S. Gov't

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Qian Ren, Jinrong Liang, Yanmei Su, Ruijing Tian, Junxian Wu, Sheng Ge, Peizhan Chen. 2025. A Causal Effect of Serum 25(OH)D Level on Appendicular Muscle Mass: Evidence From NHANES Data and Mendelian Randomization Analyses.. https://doi.org/10.1002/jcsm.13778

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