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Causal Relationship...
Causal Relationship between Obesity and Vitamin D Status: Bi-Directional Mendelian Randomization Analysis of Multiple Cohorts
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Vimaleswaran, K. S. (author)
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Berry, D. J. (author)
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Lu, C. (author)
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show more...
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Tikkanen, E. (author)
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Pilz, S. (author)
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- Lind, Lars (author)
- Uppsala universitet,Kardiovaskulär epidemiologi
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Cooper, J. D. (author)
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Dastani, Z. (author)
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Li, R. (author)
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Houston, D. K. (author)
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Wood, A. R. (author)
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- Michaëlsson, Karl (author)
- Uppsala universitet,Ortopedi
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- Vandenput, Liesbeth, 1974 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
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Zgaga, L. (author)
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- Lorentzon, Mattias, 1970 (author)
- Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research
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McCarthy, M. I. (author)
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Dupuis, J. (author)
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Kaakinen, M. (author)
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Kleber, M. E. (author)
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Jameson, K. (author)
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Arden, N. (author)
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Raitakari, O. (author)
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Viikari, J. (author)
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Lohman, K. K. (author)
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Ferrucci, L. (author)
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- Melhus, Håkan (author)
- Uppsala universitet,Klinisk farmakogenomik och osteoporos
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Ingelsson, E. (author)
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- Byberg, Liisa (author)
- Uppsala universitet,Ortopedi
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Lind, L. (author)
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- Lorentzon, Mattias, 1970 (author)
- Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research
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Salomaa, V. (author)
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Campbell, H. (author)
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Dunlop, M. (author)
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Mitchell, B. D. (author)
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Herzig, K. H. (author)
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Pouta, A. (author)
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Hartikainen, A. L. (author)
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Streeten, E. A. (author)
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Theodoratou, E. (author)
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Jula, A. (author)
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Wareham, N. J. (author)
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- Ohlsson, Claes, 1965 (author)
- Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
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Frayling, T. M. (author)
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Kritchevsky, S. B. (author)
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Spector, T. D. (author)
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Richards, J. B. (author)
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Lehtimaki, T. (author)
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Ouwehand, W. H. (author)
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Kraft, P. (author)
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Cooper, C. (author)
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Marz, W. (author)
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Power, C. (author)
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Loos, R. J. F. (author)
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Wang, T. J. (author)
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Jarvelin, M. R. (author)
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Whittaker, J. C. (author)
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Hingorani, A. D. (author)
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Hypponen, E. (author)
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(creator_code:org_t)
- 2013-02-05
- 2013
- English.
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In: Plos Medicine. - : Public Library of Science (PLoS). - 1549-1676 .- 1549-1277. ; 10:2
- Related links:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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http://kipublication...
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Abstract
Subject headings
Close
- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- body-mass index
- cardiovascular-disease risk
- genome-wide association
- genetic-variants
- instrumental variables
- d deficiency
- 25-hydroxyvitamin d
- d insufficiency
- common obesity
- prevalence
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
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Vimaleswaran, K. ...
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Berry, D. J.
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Lu, C.
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Tikkanen, E.
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Pilz, S.
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Lind, Lars
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show more...
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Cooper, J. D.
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Dastani, Z.
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Li, R.
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Houston, D. K.
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Wood, A. R.
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Michaëlsson, Kar ...
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Vandenput, Liesb ...
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Zgaga, L.
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Lorentzon, Matti ...
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McCarthy, M. I.
-
Dupuis, J.
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Kaakinen, M.
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Kleber, M. E.
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Jameson, K.
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Arden, N.
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Raitakari, O.
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Viikari, J.
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Lohman, K. K.
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Ferrucci, L.
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Melhus, Håkan
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Ingelsson, E.
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Byberg, Liisa
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Lind, L.
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Salomaa, V.
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Campbell, H.
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Dunlop, M.
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Mitchell, B. D.
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Herzig, K. H.
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Pouta, A.
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Hartikainen, A. ...
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Streeten, E. A.
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Theodoratou, E.
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Jula, A.
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Wareham, N. J.
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Ohlsson, Claes, ...
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Frayling, T. M.
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Kritchevsky, S. ...
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Spector, T. D.
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Richards, J. B.
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Lehtimaki, T.
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Ouwehand, W. H.
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Kraft, P.
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Cooper, C.
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Marz, W.
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Power, C.
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Loos, R. J. F.
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Wang, T. J.
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Jarvelin, M. R.
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Whittaker, J. C.
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Hingorani, A. D.
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Hypponen, E.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
- Articles in the publication
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Plos Medicine
- By the university
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University of Gothenburg
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Uppsala University
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Karolinska Institutet