Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts.
<h4>Background</h4>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 variab...
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2013
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oai:doaj.org-article:b73c0ace41a34f9a9e7c739cdcd2f5a92021-11-18T05:42:44ZCausal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts.1549-12771549-167610.1371/journal.pmed.1001383https://doaj.org/article/b73c0ace41a34f9a9e7c739cdcd2f5a92013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23393431/?tool=EBIhttps://doaj.org/toc/1549-1277https://doaj.org/toc/1549-1676<h4>Background</h4>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.<h4>Methods and findings</h4>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).<h4>Conclusions</h4>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.Karani S VimaleswaranDiane J BerryChen LuEmmi TikkanenStefan PilzLinda T HirakiJason D CooperZari DastaniRui LiDenise K HoustonAndrew R WoodKarl MichaëlssonLiesbeth VandenputLina ZgagaLaura M Yerges-ArmstrongMark I McCarthyJosée DupuisMarika KaakinenMarcus E KleberKaren JamesonNigel ArdenOlli RaitakariJorma ViikariKurt K LohmanLuigi FerrucciHåkan MelhusErik IngelssonLiisa BybergLars LindMattias LorentzonVeikko SalomaaHarry CampbellMalcolm DunlopBraxton D MitchellKarl-Heinz HerzigAnneli PoutaAnna-Liisa HartikainenGenetic Investigation of Anthropometric Traits-GIANT ConsortiumElizabeth A StreetenEvropi TheodoratouAntti JulaNicholas J WarehamClaes OhlssonTimothy M FraylingStephen B KritchevskyTimothy D SpectorJ Brent RichardsTerho LehtimäkiWillem H OuwehandPeter KraftCyrus CooperWinfried MärzChris PowerRuth J F LoosThomas J WangMarjo-Riitta JärvelinJohn C WhittakerAroon D HingoraniElina HyppönenPublic Library of Science (PLoS)articleMedicineRENPLoS Medicine, Vol 10, Iss 2, p e1001383 (2013) |
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Medicine R Karani S Vimaleswaran Diane J Berry Chen Lu Emmi Tikkanen Stefan Pilz Linda T Hiraki Jason D Cooper Zari Dastani Rui Li Denise K Houston Andrew R Wood Karl Michaëlsson Liesbeth Vandenput Lina Zgaga Laura M Yerges-Armstrong Mark I McCarthy Josée Dupuis Marika Kaakinen Marcus E Kleber Karen Jameson Nigel Arden Olli Raitakari Jorma Viikari Kurt K Lohman Luigi Ferrucci Håkan Melhus Erik Ingelsson Liisa Byberg Lars Lind Mattias Lorentzon Veikko Salomaa Harry Campbell Malcolm Dunlop Braxton D Mitchell Karl-Heinz Herzig Anneli Pouta Anna-Liisa Hartikainen Genetic Investigation of Anthropometric Traits-GIANT Consortium Elizabeth A Streeten Evropi Theodoratou Antti Jula Nicholas J Wareham Claes Ohlsson Timothy M Frayling Stephen B Kritchevsky Timothy D Spector J Brent Richards Terho Lehtimäki Willem H Ouwehand Peter Kraft Cyrus Cooper Winfried März Chris Power Ruth J F Loos Thomas J Wang Marjo-Riitta Järvelin John C Whittaker Aroon D Hingorani Elina Hyppönen Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts. |
| description |
<h4>Background</h4>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.<h4>Methods and findings</h4>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).<h4>Conclusions</h4>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. |
| format |
article |
| author |
Karani S Vimaleswaran Diane J Berry Chen Lu Emmi Tikkanen Stefan Pilz Linda T Hiraki Jason D Cooper Zari Dastani Rui Li Denise K Houston Andrew R Wood Karl Michaëlsson Liesbeth Vandenput Lina Zgaga Laura M Yerges-Armstrong Mark I McCarthy Josée Dupuis Marika Kaakinen Marcus E Kleber Karen Jameson Nigel Arden Olli Raitakari Jorma Viikari Kurt K Lohman Luigi Ferrucci Håkan Melhus Erik Ingelsson Liisa Byberg Lars Lind Mattias Lorentzon Veikko Salomaa Harry Campbell Malcolm Dunlop Braxton D Mitchell Karl-Heinz Herzig Anneli Pouta Anna-Liisa Hartikainen Genetic Investigation of Anthropometric Traits-GIANT Consortium Elizabeth A Streeten Evropi Theodoratou Antti Jula Nicholas J Wareham Claes Ohlsson Timothy M Frayling Stephen B Kritchevsky Timothy D Spector J Brent Richards Terho Lehtimäki Willem H Ouwehand Peter Kraft Cyrus Cooper Winfried März Chris Power Ruth J F Loos Thomas J Wang Marjo-Riitta Järvelin John C Whittaker Aroon D Hingorani Elina Hyppönen |
| author_facet |
Karani S Vimaleswaran Diane J Berry Chen Lu Emmi Tikkanen Stefan Pilz Linda T Hiraki Jason D Cooper Zari Dastani Rui Li Denise K Houston Andrew R Wood Karl Michaëlsson Liesbeth Vandenput Lina Zgaga Laura M Yerges-Armstrong Mark I McCarthy Josée Dupuis Marika Kaakinen Marcus E Kleber Karen Jameson Nigel Arden Olli Raitakari Jorma Viikari Kurt K Lohman Luigi Ferrucci Håkan Melhus Erik Ingelsson Liisa Byberg Lars Lind Mattias Lorentzon Veikko Salomaa Harry Campbell Malcolm Dunlop Braxton D Mitchell Karl-Heinz Herzig Anneli Pouta Anna-Liisa Hartikainen Genetic Investigation of Anthropometric Traits-GIANT Consortium Elizabeth A Streeten Evropi Theodoratou Antti Jula Nicholas J Wareham Claes Ohlsson Timothy M Frayling Stephen B Kritchevsky Timothy D Spector J Brent Richards Terho Lehtimäki Willem H Ouwehand Peter Kraft Cyrus Cooper Winfried März Chris Power Ruth J F Loos Thomas J Wang Marjo-Riitta Järvelin John C Whittaker Aroon D Hingorani Elina Hyppönen |
| author_sort |
Karani S Vimaleswaran |
| title |
Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts. |
| title_short |
Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts. |
| title_full |
Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts. |
| title_fullStr |
Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts. |
| title_full_unstemmed |
Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts. |
| title_sort |
causal relationship between obesity and vitamin d status: bi-directional mendelian randomization analysis of multiple cohorts. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/b73c0ace41a34f9a9e7c739cdcd2f5a9 |
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