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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Autores principales: 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
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spelling 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)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
spellingShingle 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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