Show simple item record

dc.contributor.authorVimaleswaran, Karani S.
dc.contributor.authorBerry, Diane J.
dc.contributor.authorLu, Chen
dc.contributor.authorTikkanen, Emmi
dc.contributor.authorPilz, Stefan
dc.contributor.authorHiraki, Linda T
dc.contributor.authorCooper, Jason D.
dc.contributor.authorDastani, Zari
dc.contributor.authorLi, Rui
dc.contributor.authorHouston, Denise K.
dc.contributor.authorWood, Andrew R.
dc.contributor.authorMichaëlsson, Karl
dc.contributor.authorVandenput, Liesbeth
dc.contributor.authorZgaga, Lina
dc.contributor.authorYerges-Armstrong, Laura M.
dc.contributor.authorMcCarthy, Mark I.
dc.contributor.authorDupuis, Josée
dc.contributor.authorKaakinen, Marika
dc.contributor.authorKleber, Marcus E.
dc.contributor.authorJameson, Karen
dc.contributor.authorArden, Nigel
dc.contributor.authorRaitakari, Olli
dc.contributor.authorViikari, Jorma
dc.contributor.authorLohman, Kurt K.
dc.contributor.authorFerrucci, Luigi
dc.contributor.authorMelhus, Håkan
dc.contributor.authorIngelsson, Erik
dc.contributor.authorByberg, Liisa
dc.contributor.authorLind, Lars
dc.contributor.authorLorentzon, Mattias
dc.contributor.authorSalomaa, Veikko
dc.contributor.authorCampbell, Harry
dc.contributor.authorDunlop, Malcolm
dc.contributor.authorMitchell, Braxton D.
dc.contributor.authorHerzig, Karl-Heinz
dc.contributor.authorPouta, Anneli
dc.contributor.authorHartikainen, Anna-Liisa
dc.contributor.authorStreeten, Elizabeth A.
dc.contributor.authorTheodoratou, Evropi
dc.contributor.authorJula, Antti
dc.contributor.authorWareham, Nicholas J.
dc.contributor.authorOhlsson, Claes
dc.contributor.authorFrayling, Timothy M.
dc.contributor.authorKritchevsky, Stephen B.
dc.contributor.authorSpector, Timothy D.
dc.contributor.authorRichards, J. Brent
dc.contributor.authorLehtimäki, Terho
dc.contributor.authorOuwehand, Willem H.
dc.contributor.authorKraft, Peter
dc.contributor.authorCooper, Cyrus
dc.contributor.authorMärz, Winfried
dc.contributor.authorPower, Chris
dc.contributor.authorLoos, Ruth J. F.
dc.contributor.authorWang, Thomas Jue-Fuu
dc.contributor.authorJärvelin, Marjo-Riitta
dc.contributor.authorWhittaker, John C.
dc.contributor.authorHingorani, Aroon D.
dc.contributor.authorHyppönen, Elina
dc.contributor.authorGenetic Investigation of Anthropometric Traits (GIANT) consortium
dc.date.accessioned2013-05-09T18:57:42Z
dc.date.issued2013
dc.identifier.citationVimaleswaran, Karani S., Diane J. Berry, Chen Lu, Emmi Tikkanen, Stefan Pilz, Linda T. Hiraki, Jason D. Cooper, and et al. 2013. Causal relationship between obesity and vitamin D status: Bi-directional Mendelian randomization analysis of multiple cohorts. PLoS Medicine 10(2): e1001383.en_US
dc.identifier.issn1549-1277en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10613670
dc.description.abstractBackground: 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. Please see later in the article for the Editors' Summary.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pmed.1001383en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3564800/pdf/en_US
dash.licenseLAA
dc.subjectbiologyen_US
dc.subjectgeneticsen_US
dc.subjectpopulation geneticsen_US
dc.subjectgenetic polymorphismen_US
dc.subjectpopulation biologyen_US
dc.subjectepidemiologyen_US
dc.subjectgenetic epidemiologyen_US
dc.titleCausal Relationship Between Obesity and Vitamin D Status: Bi-Directional Mendelian Randomization Analysis of Multiple Cohortsen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS Medicineen_US
dash.depositing.authorWang, Thomas Jue-Fuu
dc.date.available2013-05-09T18:57:42Z
dc.identifier.doi10.1371/journal.pmed.1001383*
dash.authorsorderedfalse
dash.contributor.affiliatedHiraki, Linda T.
dash.contributor.affiliatedWang, Thomas Jue-Fuu


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record