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    Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts.

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    Author
    Vimaleswaran, KS; Berry, DJ; Lu, C; Tikkanen, E; Pilz, S; Hiraki, LT; Cooper, JD; Dastani, Z; Li, R; Houston, DK; ...
    Date
    2013
    Source Title
    PLoS Medicine
    Publisher
    Public Library of Science (PLoS)
    University of Melbourne Author/s
    Goddard, Michael
    Affiliation
    Agriculture and Food Systems
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Vimaleswaran, K. S., Berry, D. J., Lu, C., Tikkanen, E., Pilz, S., Hiraki, L. T., Cooper, J. D., Dastani, Z., Li, R., Houston, D. K., Wood, A. R., Michaëlsson, K., Vandenput, L., Zgaga, L., Yerges-Armstrong, L. M., McCarthy, M. I., Dupuis, J., Kaakinen, M., Kleber, M. E. ,... Hyppönen, E. (2013). Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts.. PLoS Med, 10 (2), pp.e1001383-. https://doi.org/10.1371/journal.pmed.1001383.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/253780
    DOI
    10.1371/journal.pmed.1001383
    Open Access at PMC
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3564800
    Abstract
    BACKGROUND: Obesity is associated with vitamin D deficiency, and both are areas of active public health concern. We explored the causality and direction of the relationship between body mass index (BMI) and 25-hydroxyvitamin D [25(OH)D] using genetic markers as instrumental variables (IVs) in bi-directional Mendelian randomization (MR) analysis. METHODS AND FINDINGS: We used information from 21 adult cohorts (up to 42,024 participants) with 12 BMI-related SNPs (combined in an allelic score) to produce an instrument for BMI and four SNPs associated with 25(OH)D (combined in two allelic scores, separately for genes encoding its synthesis or metabolism) as an instrument for vitamin D. Regression estimates for the IVs (allele scores) were generated within-study and pooled by meta-analysis to generate summary effects. Associations between vitamin D scores and BMI were confirmed in the Genetic Investigation of Anthropometric Traits (GIANT) consortium (n = 123,864). Each 1 kg/m(2) higher BMI was associated with 1.15% lower 25(OH)D (p = 6.52×10⁻²⁷). The BMI allele score was associated both with BMI (p = 6.30×10⁻⁶²) and 25(OH)D (-0.06% [95% CI -0.10 to -0.02], p = 0.004) in the cohorts that underwent meta-analysis. The two vitamin D allele scores were strongly associated with 25(OH)D (p≤8.07×10⁻⁵⁷ for both scores) but not with BMI (synthesis score, p = 0.88; metabolism score, p = 0.08) in the meta-analysis. A 10% higher genetically instrumented BMI was associated with 4.2% lower 25(OH)D concentrations (IV ratio: -4.2 [95% CI -7.1 to -1.3], p = 0.005). No association was seen for genetically instrumented 25(OH)D with BMI, a finding that was confirmed using data from the GIANT consortium (p≥0.57 for both vitamin D scores). CONCLUSIONS: On the basis of a bi-directional genetic approach that limits confounding, our study suggests that a higher BMI leads to lower 25(OH)D, while any effects of lower 25(OH)D increasing BMI are likely to be small. Population level interventions to reduce BMI are expected to decrease the prevalence of vitamin D deficiency.

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