دورية أكاديمية
Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts
| العنوان: | Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts |
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| المؤلفون: | Vimaleswaran KS, Berry DJ, Lu C, Tikkanen E, Pilz S, Hiraki LT, Cooper JD, Dastani Z, Li R, Houston DK, Wood AR, Michaëlsson K, Vandenput L, Zgaga L, Yerges-Armstrong LM, McCarthy MI, Dupuis J, Kaakinen M, Kleber ME, Jameson K, Arden N, Raitakari O, Viikari J, Lohman KK, Ferrucci L, Melhus H, Ingelsson E, Byberg L, Lind L, Lorentzon M, Salomaa V, Campbell H, Dunlop M, Mitchell BD, Herzig KH, Pouta A, Hartikainen AL, Genetic Investigation of Anthropometric Traits-GIANT Consortium, Streeten EA, Theodoratou E, Jula A, Wareham NJ, Ohlsson C, Frayling TM, Kritchevsky SB, Spector TD, Richards JB, Lehtimäki T, Ouwehand WH, Kraft P, Cooper C, März W, Power C, Loos RJ, Wang TJ, Järvelin MR, Whittaker JC, Hingorani AD, Hyppönen E |
| بيانات النشر: | Public Library of Science PLoS Uppsala universitet, Ortopedi Uppsala universitet, Klinisk farmakogenomik och osteoporos Uppsala universitet, Kardiovaskulär epidemiologi Public Library of Science (PLoS) |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | demo, psy |
| الوصف: | 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 ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | http://hdl.handle.net/10863/6687Test |
| الإتاحة: | http://hdl.handle.net/10863/6687Test |
| حقوق: | undefined |
| رقم الانضمام: | edsbas.A7ADE5D0 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |