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The Relationship Between Obesity and Vitamin D Deficiency: Causation Determined?

Multiple investigations have evaluated the relationship between obesity and vitamin D deficiency, two modifiable factors that contribute to the risk of several chronic diseases. While such studies have identified a strong association between these phenotypes, it has been difficult to determine causality and the direction of the association. Through a series of sophisticated genetic analyses including bi-directional Mendelian randomization (MR), results from Vimaleswaran et al. have highlighted potentially important insights regarding the link between obesity, as assessed by BMI, and vitamin D deficiency. Using meta-analysis approaches in approximately 42,000 participants of D-CarDia, the authors observed that each unit increase in BMI was associated with a 1.15% decrease in 25-hydroxyvitamin D [25(OH)D]. In order to infer causality, their findings were extended by MR using previously established BMI-related (n = 12) and vitamin D–related (n = 4) single nucleotide polymorphisms in order to generate allele scores for the analyses. These analyses revealed that while the BMI allele score was significantly associated with reduced 25(OH)D levels (-0.06% [95% CI -0.10 to -0.02%], P = 0.004), neither the vitamin D synthesis or metabolism allele scores were associated with BMI (0.01 [-0.17 to 0.20], P = 0.88 and 0.17 [-0.02 to 0.35], P = 0.08, respectively). Using the instrumental variable (IV) ratio method, it was observed that each 10% increase in BMI led to a 4.2% decrease in 25(OH)D levels. In contrast, IV analyses did not provide evidence that 25(OH)D levels significantly affected BMI. Follow-up analyses using data from the Genetic Investigation of Anthropometric Traits (GIANT) consortium confirmed the lack of association between vitamin D allele scores and BMI. Together, these results suggest that an increase …

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  1. doi: 10.2337/db13-dd08 Diabetes vol. 62 no. 8 2993-2994
  1. Free via Open Access: OA