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

K.S. Vimaleswaran, D.J. Berry, C. Lu, E. Tikkanen, S. Pilz, L.T. Hiraki, J.D. Cooper, Z. Dastani, R. Li, D.K. Houston, A.R. Wood, K. Michaëlsson, L. Vandenput, L. Zgaga, L.M. Yerges-Armstrong, M.I. McCarthy, J. Dupuis, M. Kaakinen, M.E. Kleber, K. JamesonN. Arden, O. Raitakari, J. Viikari, K.K. Lohman, L. Ferrucci, H. Melhus, E. Ingelsson, L. Byberg, L. Lind, M. Lorentzon, V. Salomaa, H. Campbell, M. Dunlop, B.D. Mitchell, K.H. Herzig, A. Pouta, A.L. Hartikainen, J.J. Hottenga, E.J.C. de Geus, G. Willemsen, D.I. Boomsma, B.W.J.H. Penninx, A.G. Uitterlinden, P.M. Visscher, C.M. van Duijn, E.A. Streeten, E. Theodoratou, A. Jula, N.J. Wareham, C. Ohlsson, T.M. Frayling, S.B. Kritchevsky, T.D. Spector, J.B. Richards, T. Lehtimäki, W.H. Ouwehand, P. Kraft, C. Cooper, W. März, C. Power, R.J. Loos, T.J. Wang, M.R. Järvelin, J.C. Whittaker, A.D. Hingorani, E. Hyppönen

Research output: Contribution to JournalArticleAcademicpeer-review

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
Original languageEnglish
Article numbere1001383
JournalPLoS Medicine
Volume10
Issue number2
DOIs
Publication statusPublished - 2013

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