Dataset Information

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

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?²?). The BMI allele score was associated both with BMI (p?=?6.30×10??²) 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??? 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.

SUBMITTER: Vimaleswaran KS

PROVIDER: S-EPMC3564800 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

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

Vimaleswaran Karani S KS Berry Diane J DJ Lu Chen C Tikkanen Emmi E Pilz Stefan S Hiraki Linda T LT Cooper Jason D JD Dastani Zari Z Li Rui R Houston Denise K DK Wood Andrew R AR Michaëlsson Karl K Vandenput Liesbeth L Zgaga Lina L Yerges-Armstrong Laura M LM McCarthy Mark I MI Dupuis Josée J Kaakinen Marika M Kleber Marcus E ME Jameson Karen K Arden Nigel N Raitakari Olli O Viikari Jorma J Lohman Kurt K KK Ferrucci Luigi L Melhus Håkan H Ingelsson Erik E Byberg Liisa L Lind Lars L Lorentzon Mattias M Salomaa Veikko V Campbell Harry H Dunlop Malcolm M Mitchell Braxton D BD Herzig Karl-Heinz KH Pouta Anneli A Hartikainen Anna-Liisa AL Streeten Elizabeth A EA Theodoratou Evropi E Jula Antti A Wareham Nicholas J NJ Ohlsson Claes C Frayling Timothy M TM Kritchevsky Stephen B SB Spector Timothy D TD Richards J Brent JB Lehtimäki Terho T Ouwehand Willem H WH Kraft Peter P Cooper Cyrus C März Winfried W Power Chris C Loos Ruth J F RJ Wang Thomas J TJ Järvelin Marjo-Riitta MR Whittaker John C JC Hingorani Aroon D AD Hyppönen Elina E

PLoS medicine 20130205 2

<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 alleli ...[more]

PMID: 23393431

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Dataset Information

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

Background

Methods and findings

Conclusions

Publications

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

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