Lee Young, Seo Je Hyun, Lee Junyong, Kim Hwa Sun
Veterans Medical Research Institute, Veterans Health Service Medical Center, Seoul 05368, Republic of Korea.
Department of Family Medicine, Veterans Health Service Medical Center, Seoul 05368, Republic of Korea.
Biomedicines. 2025 Mar 15;13(3):723. doi: 10.3390/biomedicines13030723.
Individuals with metabolic syndrome (MetS) present reduced 25(OH)D levels. We performed a two-sample Mendelian randomization (MR) study to investigate whether causal relationships exist between 25(OH)D levels and MetS/MetS risk traits, including waist circumference, body mass index (BMI), hypertension (systolic/diastolic blood pressure), triglyceride, high-density lipoprotein cholesterol, and glucose levels. We employed genetic variants related to 25(OH)D levels from the SUNLIGHT Consortium and a European genome-wide association study meta-analysis, including UK Biobank (UKB) data, as well as variants for MetS and MetS risk traits from UKB and multiple European consortia. Several MR methods were used, i.e., inverse-variance weighted, weighted median, and MR-Egger regression. Heterogeneity and horizontal pleiotropy analyses were performed to ensure the stability of candidate single-nucleotide polymorphisms (SNPs) as the instrumental variable. We first conducted univariable MR to investigate the relationship between 25(OH)D levels and MetS, including its related risk traits, and subsequently performed multivariable MR to adjust for potential confounders. This study did not provide evidence of a causal relationship between 25(OH)D levels and MetS/MetS risk traits. However, we found that several risk traits of MetS, such as waist circumference, BMI, and TG, had an inverse-causal relationship with 25(OH)D levels, suggesting that 25(OH)D levels could be secondary consequences of metabolic illnesses. We identified no causal relationship between 25(OH)D levels and MetS/MetS risk factors. However, 25(OH)D levels may result from MetS traits.
患有代谢综合征（MetS）的个体25(OH)D水平降低。我们进行了一项两样本孟德尔随机化（MR）研究，以调查25(OH)D水平与MetS/MetS风险特征之间是否存在因果关系，这些特征包括腰围、体重指数（BMI）、高血压（收缩压/舒张压）、甘油三酯、高密度脂蛋白胆固醇和血糖水平。我们采用了来自阳光财团的与25(OH)D水平相关的基因变异以及一项欧洲全基因组关联研究的荟萃分析，其中包括英国生物银行（UKB）的数据，还有来自UKB和多个欧洲联盟的MetS及MetS风险特征的变异。使用了几种MR方法，即逆方差加权法、加权中位数法和MR-Egger回归法。进行了异质性和水平多效性分析，以确保候选单核苷酸多态性（SNP）作为工具变量的稳定性。我们首先进行单变量MR，以研究25(OH)D水平与MetS之间的关系，包括其相关风险特征，随后进行多变量MR以调整潜在的混杂因素。本研究没有提供25(OH)D水平与MetS/MetS风险特征之间存在因果关系的证据。然而，我们发现MetS的几个风险特征，如腰围、BMI和甘油三酯，与25(OH)D水平呈反向因果关系，这表明25(OH)D水平可能是代谢疾病的次要后果。我们没有发现25(OH)D水平与MetS/MetS风险因素之间存在因果关系。然而，25(OH)D水平可能是由MetS特征导致的。
