Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts.
Details
State: Public
Version: author
Serval ID
serval:BIB_84BDDA1FD326
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts.
Journal
PLOS Medicine
Working group(s)
Genetic Investigation of Anthropometric Traits-GIANT Consortium
Contributor(s)
Speliotes E.K., Willer C.J., Berndt S.I., Monda K.L., Thorleifsson G., Jackson A.U., Allen H.L., Lindgren C.M., Jian'an L., Mägi R., Randall J.C., Vedantam S., Winkler T.W., Qi L., Workalemahu T., Heid I.M., Steinthorsdottir V., Stringham H.M., Weedon M.N., Wheeler E., Wood A.R., Ferreira T., Weyant R.J., Segrè A.V., Estrada K., Liang L., Nemesh J., Park J.H., Gustafsson S., Kilpeläinen T.O., Yang J., Bouatia-Naji N., Tõnu E., Feitosa M.F., Kutalik Z., Mangino M., Raychaudhuri S., Scherag A., Smith A.V., Welch R., Zhao J.H., Aben K.K., Absher D.M., Amin N., Dixon A.L., Fisher E., Glazer N.L., Goddard M.E., Heard-Costa N.L., Hoesel V., Hottenga J.J., Johansson Å., Johnson T., Ketkar S., Lamina C., Li S., Moffatt M.F., Myers R.H., Narisu N., Perry J.R., Peters M.J., Preuss M., Ripatti S., Rivadeneira F., Sandholt C., Scott L.J., Timpson N.J., Tyrer J.P., van Wingerden S., Watanabe R.M., White C.C., Wiklund F., Barlassina C., Chasman D.I., Cooper M.N., Jansson J.O., Lawrence R.W., Pellikka N., Prokopenko I., Shi J., Thiering E., Alavere H., Alibrandi M.T., Almgren P., Arnold A.M., Aspelund T., Atwood L.D., Balkau B., Balmforth A.J., Bennett A.J., Ben-Shlomo Y., Bergman R.N., Bergmann S., Biebermann H., Blakemore A.I., Boes T., Bonnycastle L.L., Bornstein S.R., Brown M.J., Buchanan T.A., Busonero F., Campbell H., Cappuccio F.P., Cavalcanti-Proença C., Chen Y.D., Chen C.M., Chines P.S., Clarke R., Coin L., Connell J., Day I.N., Heijer M., Duan J., Ebrahim S., Elliott P., Elosua R., Eiriksdottir G., Erdos M.R., Eriksson J.G., Facheris M.F., Felix S.B., Fischer-Posovszky P., Folsom A.R., Friedrich N., Freimer N.B., Fu M., Gaget S., Gejman P.V., Geus E.J., Gieger C., Gjesing A.P., Goel A., Goyette P., Grallert H., Gräßler J., Greenawalt D.M., Groves C.J., Gudnason V., Guiducci C., Hartikainen A.L., Hassanali N., Hall A.S., Havulinna A.S., Hayward C., Heath A.C., Hengstenberg C., Hicks A.A., Hinney A., Hofman A., Homuth G., Hui J., Igl W., Iribarren C., Isomaa B., Jacobs K.B., Jarick I., Jewell E., John U., Jørgensen T., Jousilahti P., Jula A., Kaakinen M., Kajantie E., Kaplan L.M., Kathiresan S., Kettunen J., Kinnunen L., Knowles J.W., Kolcic I., König I.R., Koskinen S., Kovacs P., Kuusisto J., Kraft P., Kvaløy K., Laitinen J., Lantieri O., Lanzani C., Launer L.J., Lecoeur C., Lehtimäki T., Lettre G., Liu J., Lokki M.L., Lorentzon M., Luben R.N., Ludwig B., Manunta P., Marek D., Marre M., Martin N.G., McArdle W.L., McCarthy A., McKnight B., Meitinger T., Melander O., Meyre D., Midthjell K., Montgomery G.W., Morken M.A., Morris A.P., Mulic R., Ngwa J.S., Nelis M., Neville M.J., Nyholt D.R., O'Donnell C.J., O'Rahilly S., Ong K.K., Oostra B., Paré G., Parker A.N., Perola M., Pichler I., Pietiläinen K.H., Platou C.G., Polasek O., Pouta A., Rafelt S., Raitakari O., Rayner N.W., Ridderstråle M., Rief W., Ruokonen A., Robertson N.R., Rzehak P., Salomaa V., Sanders A.R., Sandhu M.S., Sanna S., Saramies J., Savolainen M.J., Scherag S., Schipf S., Schreiber S., Schunkert H., Silander K., Sinisalo J., Siscovick D.S., Smit J.H., Soranzo N., Sovio U., Stephens J., Surakka I., Swift AJ., Tammesoo M.L., Tardif J.C., Teder-Laving M., Teslovich T.M., Thompson J.R., Thomson B., Tönjes A., Tuomi T., van Meurs J.B., van Ommen G.J., Vatin V., Viikari J., Visvikis-Siest S., Vitart V., Vogel C.I., Voight B.F., Waite L.L., Wallaschofski H., Walters G.B., Widen E., Wiegand S., Wild S.H., Willemsen G., Witte D.R., Witteman J.C., Xu J., Zhang Q., Zgaga L., Ziegler A., Zitting P., Beilby J.P., Farooqi I.S., Hebebrand J., Huikuri H.V., James AL., Kähönen M., Levinson D.F., Macciardi F., Nieminen M.S., Ohlsson C., Palmer L.J., Ridker P.M., Stumvoll M., Beckmann J.S., Boeing H., Boerwinkle E., Boomsma D.I., Caulfield M.J., Chanock S.J., Collins F.S., Cupples L.A., Smith G.D., Erdmann J., Froguel P., Grönberg H., Gyllensten U., Hall P., Hansen T., Harris T.B., Hattersley A.T., Hayes R.B., Heinrich J., Hu F.B., Hveem K., Illig T., Jarvelin M.R., Kaprio J., Karpe F., Khaw K.T., Kiemeney L.A., Krude H., Laakso M., Lawlor D.A., Metspalu A., Munroe P.B., Ouwehand W.H., Pedersen O., Penninx B.W., Peters A., Pramstaller P.P., Quertermous T., Reinehr T., Rissanen A., Rudan I., Samani N.J., Schwarz P.E., Shuldiner A.R., Spector T.D., Tuomilehto J., Uda M., Uitterlinden A., Valle T.T., Wabitsch M., Waeber G., Wareham N.J., Watkins H., Wilson J.F., Wright A.F., Zillikens M.C., Chatterjee N., McCarroll S.A., Purcell S., Schadt E.E., Visscher P.M., Assimes T.L., Borecki I.B., Deloukas P., Fox C.S., Groop L.C., Haritunians T., Hunter D.J., Kaplan R.C., Mohlke K.L., O'Connell J.R., Peltonen L., Schlessinger D., Strachan D.P., van Duijn C.M., Wichmann H.E., Frayling T.M., Thorsteinsdottir U., Abecasis G.R., Barroso I., Boehnke M., Stefansson K., North K.E., McCarthy M.I., Hirschhorn J.N., Ingelsson E., Loos R.J.
ISSN
1549-1676 (Electronic)
ISSN-L
1549-1277
Publication state
Published
Issued date
02/2013
Volume
10
Number
2
Pages
e1001383
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
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 = 6.52×10⁻²⁷). 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).
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.
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 = 6.52×10⁻²⁷). 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).
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.
Pubmed
Web of science
Open Access
Yes
Create date
28/03/2013 13:07
Last modification date
20/08/2019 15:44
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