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. Jameson; N. 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

doi:10.1371/journal.pmed.1001383

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

Biological Psychology

Research output: Contribution to Journal › Article › Academic › peer-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 language	English
Article number	e1001383
Journal	PLoS Medicine
Volume	10
Issue number	2
DOIs	https://doi.org/10.1371/journal.pmed.1001383
Publication status	Published - 2013

Cohort Studies

Netherlands Twin Register (NTR)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1371/journal.pmed.1001383

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Vimaleswaran, K. S., Berry, D. J., Lu, C., Tikkanen, E., Pilz, S., Hiraki, L. T., Cooper, J. D., Dastani, Z., Li, R., Houston, D. K., Wood, A. R., Michaëlsson, K., Vandenput, L., Zgaga, L., Yerges-Armstrong, L. M., McCarthy, M. I., Dupuis, J., Kaakinen, M., Kleber, M. E., ... Hyppönen, E. (2013). Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts. PLoS Medicine, 10(2), Article e1001383. https://doi.org/10.1371/journal.pmed.1001383

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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",

author = "K.S. Vimaleswaran and D.J. Berry and C. Lu and E. Tikkanen and S. Pilz and L.T. Hiraki and J.D. Cooper and Z. Dastani and R. Li and D.K. Houston and A.R. Wood and K. Micha{\"e}lsson and L. Vandenput and L. Zgaga and L.M. Yerges-Armstrong and M.I. McCarthy and J. Dupuis and M. Kaakinen and M.E. Kleber and K. Jameson and N. Arden and O. Raitakari and J. Viikari and K.K. Lohman and L. Ferrucci and H. Melhus and E. Ingelsson and L. Byberg and L. Lind and M. Lorentzon and V. Salomaa and H. Campbell and M. Dunlop and B.D. Mitchell and K.H. Herzig and A. Pouta and A.L. Hartikainen and J.J. Hottenga and {de Geus}, E.J.C. and G. Willemsen and D.I. Boomsma and B.W.J.H. Penninx and A.G. Uitterlinden and P.M. Visscher and {van Duijn}, C.M. and E.A. Streeten and E. Theodoratou and A. Jula and N.J. Wareham and C. Ohlsson and T.M. Frayling and S.B. Kritchevsky and T.D. Spector and J.B. Richards and T. Lehtim{\"a}ki and W.H. Ouwehand and P. Kraft and C. Cooper and W. M{\"a}rz and C. Power and R.J. Loos and T.J. Wang and M.R. J{\"a}rvelin and J.C. Whittaker and A.D. Hingorani and E. Hypp{\"o}nen",

year = "2013",

doi = "10.1371/journal.pmed.1001383",

language = "English",

volume = "10",

journal = "PLoS Medicine",

issn = "1549-1277",

publisher = "Public Library of Science",

number = "2",

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Vimaleswaran, KS, Berry, DJ, Lu, C, Tikkanen, E, Pilz, S, Hiraki, LT, Cooper, JD, Dastani, Z, Li, R, Houston, DK, Wood, AR, Michaëlsson, K, Vandenput, L, Zgaga, L, Yerges-Armstrong, LM, McCarthy, MI, Dupuis, J, Kaakinen, M, Kleber, ME, Jameson, K, Arden, N, Raitakari, O, Viikari, J, Lohman, KK, Ferrucci, L, Melhus, H, Ingelsson, E, Byberg, L, Lind, L, Lorentzon, M, Salomaa, V, Campbell, H, Dunlop, M, Mitchell, BD, Herzig, KH, Pouta, A, Hartikainen, AL, Hottenga, JJ , de Geus, EJC, Willemsen, G, Boomsma, DI, Penninx, BWJH, Uitterlinden, AG, Visscher, PM, van Duijn, CM, Streeten, EA, Theodoratou, E, Jula, A, Wareham, NJ, Ohlsson, C, Frayling, TM, Kritchevsky, SB, Spector, TD, Richards, JB, Lehtimäki, T, Ouwehand, WH, Kraft, P, Cooper, C, März, W, Power, C, Loos, RJ, Wang, TJ, Järvelin, MR, Whittaker, JC, Hingorani, AD & Hyppönen, E 2013, 'Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts', PLoS Medicine, vol. 10, no. 2, e1001383. https://doi.org/10.1371/journal.pmed.1001383

TY - JOUR

T1 - Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts

AU - Vimaleswaran, K.S.

AU - Berry, D.J.

AU - Lu, C.

AU - Tikkanen, E.

AU - Pilz, S.

AU - Hiraki, L.T.

AU - Cooper, J.D.

AU - Dastani, Z.

AU - Li, R.

AU - Houston, D.K.

AU - Wood, A.R.

AU - Michaëlsson, K.

AU - Vandenput, L.

AU - Zgaga, L.

AU - Yerges-Armstrong, L.M.

AU - McCarthy, M.I.

AU - Dupuis, J.

AU - Kaakinen, M.

AU - Kleber, M.E.

AU - Jameson, K.

AU - Arden, N.

AU - Raitakari, O.

AU - Viikari, J.

AU - Lohman, K.K.

AU - Ferrucci, L.

AU - Melhus, H.

AU - Ingelsson, E.

AU - Byberg, L.

AU - Lind, L.

AU - Lorentzon, M.

AU - Salomaa, V.

AU - Campbell, H.

AU - Dunlop, M.

AU - Mitchell, B.D.

AU - Herzig, K.H.

AU - Pouta, A.

AU - Hartikainen, A.L.

AU - Hottenga, J.J.

AU - de Geus, E.J.C.

AU - Willemsen, G.

AU - Boomsma, D.I.

AU - Penninx, B.W.J.H.

AU - Uitterlinden, A.G.

AU - Visscher, P.M.

AU - van Duijn, C.M.

AU - Streeten, E.A.

AU - Theodoratou, E.

AU - Jula, A.

AU - Wareham, N.J.

AU - Ohlsson, C.

AU - Frayling, T.M.

AU - Kritchevsky, S.B.

AU - Spector, T.D.

AU - Richards, J.B.

AU - Lehtimäki, T.

AU - Ouwehand, W.H.

AU - Kraft, P.

AU - Cooper, C.

AU - März, W.

AU - Power, C.

AU - Loos, R.J.

AU - Wang, T.J.

AU - Järvelin, M.R.

AU - Whittaker, J.C.

AU - Hingorani, A.D.

AU - Hyppönen, E.

PY - 2013

Y1 - 2013

N2 - 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

AB - 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

U2 - 10.1371/journal.pmed.1001383

DO - 10.1371/journal.pmed.1001383

M3 - Article

SN - 1549-1277

VL - 10

JO - PLoS Medicine

JF - PLoS Medicine

IS - 2

M1 - e1001383

ER -

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

Abstract

Cohort Studies

UN SDGs

Access to Document

Persistent URL (handle)

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