Authors
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 JF Loos, Thomas J Wang, Marjo-Riitta Järvelin, John C Whittaker, Aroon D Hingorani, Elina Hyppönen
Publication date
2013/2/5
Journal
PLoS medicine
Volume
10
Issue
2
Pages
e1001383
Publisher
Public Library of Science
Description
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/m2 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 …
Total citations
Scholar articles
KS Vimaleswaran, DJ Berry, C Lu, E Tikkanen, S Pilz… - PLoS medicine, 2013