Vitamin D and risk of pregnancy related hypertensive disorders: mendelian randomisation study

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorMAGNUS, Maria C.
dc.contributor.authorMILIKU, Kozeta
dc.contributor.authorBAUER, Anna
dc.contributor.authorENGEL, Stephanie M.
dc.contributor.authorFELIX, Janine F.
dc.contributor.authorJADDOE, Vincent W. V.
dc.contributor.authorLAWLOR, Debbie A.
dc.contributor.authorLONDON, Stephanie J.
dc.contributor.authorMAGNUS, Per
dc.contributor.authorMCGINNIS, Ralph
dc.contributor.authorNYSTAD, Wenche
dc.contributor.authorPAGE, Christian M.
dc.contributor.authorRIVADENEIRA, Fernando
dc.contributor.authorSTENE, Lars C.
dc.contributor.authorTAPIA, German
dc.contributor.authorWILLIAMS, Nicholas
dc.contributor.authorBONILLA, Carolina
dc.contributor.authorFRASER, Abigail
dc.date.accessioned2018-09-13T15:32:36Z
dc.date.available2018-09-13T15:32:36Z
dc.date.issued2018
dc.description.abstractOBJECTIVE To use mendelian randomisation to investigate whether 25-hydroxyvitamin D concentration has a causal effect on gestational hypertension or pre-eclampsia. DESIGN One and two sample mendelian randomisation analyses. SETTING Two European pregnancy cohorts (Avon Longitudinal Study of Parents and Children, and Generation R Study), and two case-control studies (subgroup nested within the Norwegian Mother and Child Cohort Study, and the UK Genetics of Pre-eclampsia Study). PARTICIPANTS 7389 women in a one sample mendelian randomisation analysis (751 with gestational hypertension and 135 with pre-eclampsia), and 3388 pre-eclampsia cases and 6059 controls in a two sample mendelian randomisation analysis. EXPOSURES Single nucleotide polymorphisms in genes associated with vitamin D synthesis (rs10741657 and rs12785878) and metabolism (rs6013897 and rs2282679) were used as instrumental variables. MAIN OUTCOME MEASURES Gestational hypertension and pre-eclampsia defined according to the International Society for the Study of Hypertension in Pregnancy. RESULTS In the conventional multivariable analysis, the relative risk for pre-eclampsia was 1.03 (95% confidence interval 1.00 to 1.07) per 10% decrease in 25-hydroxyvitamin D level, and 2.04 (1.02 to 4.07) for 25-hydroxyvitamin D levels < 25 nmol/L compared with >= 75 nmol/L. No association was found for gestational hypertension. The one sample mendelian randomisation analysis using the total genetic risk score as an instrument did not provide strong evidence of a linear effect of 25-hydroxyvitamin D on the risk of gestational hypertension or pre-eclampsia: odds ratio 0.90 (95% confidence interval 0.78 to 1.03) and 1.19 (0.92 to 1.52) per 10% decrease, respectively. The two sample mendelian randomisation estimate gave an odds ratio for preeclampsia of 0.98 (0.89 to 1.07) per 10% decrease in 25-hydroxyvitamin D level, an odds ratio of 0.96 (0.80 to 1.15) per unit increase in the log(odds) of 25-hydroxyvitamin D level < 75 nmol/L, and an odds ratio of 0.93 (0.73 to 1.19) per unit increase in the log(odds) of 25-hydroxyvitamin D levels < 50 nmol/L. CONCLUSIONS No strong evidence was found to support a causal effect of vitamin D status on gestational hypertension or pre-eclampsia. Future mendelian randomisation studies with a larger number of women with preeclampsia or more genetic instruments that would increase the proportion of 25-hydroxyvitamin D levels explained by the instrument are needed.
dc.description.indexMEDLINE
dc.description.sponsorshipEuropean Union's Horizon 2020 research and innovation programme [633595, 733206]
dc.description.sponsorshipResearch Council of Norway through its Centres of Excellence funding scheme [262700]
dc.identifier.citationBMJ-BRITISH MEDICAL JOURNAL, v.361, article ID k2167, 9p, 2018
dc.identifier.doi10.1136/bmj.k2167
dc.identifier.issn1756-1833
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/28501
dc.language.isoeng
dc.publisherBMJ PUBLISHING GROUP
dc.relation.ispartofBMJ-British Medical Journal
dc.rightsopenAccess
dc.rights.holderCopyright BMJ PUBLISHING GROUP
dc.subject.othergenome-wide association
dc.subject.other1,25-dihydroxyvitamin d-3
dc.subject.otherneonatal outcomes
dc.subject.otherd supplementation
dc.subject.otherpreeclampsia
dc.subject.otherwomen
dc.subject.otherepidemiology
dc.subject.othercohort
dc.subject.otherdeterminants
dc.subject.othermetaanalysis
dc.subject.wosMedicine, General & Internal
dc.titleVitamin D and risk of pregnancy related hypertensive disorders: mendelian randomisation study
dc.typearticle
dc.type.categoryoriginal article
dc.type.versionpublishedVersion
dspace.entity.typePublication
hcfmusp.affiliation.countryEstados Unidos
hcfmusp.affiliation.countryNoruega
hcfmusp.affiliation.countryInglaterra
hcfmusp.affiliation.countryHolanda
hcfmusp.affiliation.countryisono
hcfmusp.affiliation.countryisonl
hcfmusp.affiliation.countryisous
hcfmusp.affiliation.countryisogb
hcfmusp.author.externalMAGNUS, Maria C.:Univ Bristol, Med Res Council Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England; Univ Bristol Sch Med, Dept Populat Hlth Sci, Bristol, Avon, England; Norwegian Inst Publ Hlth, Ctr Fertil & Hlth, Oslo, Norway
hcfmusp.author.externalMILIKU, Kozeta:Erasmus MC, Univ Med Ctr Rotterdam, Generat Study Grp R, Rotterdam, Netherlands; Erasmus MC, Univ Med Ctr Rotterdam, Dept Pediat, Rotterdam, Netherlands; Erasmus MC, Univ Med Ctr Rotterdam, Dept Epidemiol, Rotterdam, Netherlands
hcfmusp.author.externalBAUER, Anna:Univ N Carolina, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27515 USA
hcfmusp.author.externalENGEL, Stephanie M.:Univ N Carolina, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27515 USA
hcfmusp.author.externalFELIX, Janine F.:Erasmus MC, Univ Med Ctr Rotterdam, Generat Study Grp R, Rotterdam, Netherlands; Erasmus MC, Univ Med Ctr Rotterdam, Dept Pediat, Rotterdam, Netherlands; Erasmus MC, Univ Med Ctr Rotterdam, Dept Epidemiol, Rotterdam, Netherlands
hcfmusp.author.externalJADDOE, Vincent W. V.:Erasmus MC, Univ Med Ctr Rotterdam, Generat Study Grp R, Rotterdam, Netherlands; Erasmus MC, Univ Med Ctr Rotterdam, Dept Pediat, Rotterdam, Netherlands; Erasmus MC, Univ Med Ctr Rotterdam, Dept Epidemiol, Rotterdam, Netherlands
hcfmusp.author.externalLAWLOR, Debbie A.:Univ Bristol, Med Res Council Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England; Univ Bristol Sch Med, Dept Populat Hlth Sci, Bristol, Avon, England; Univ Hosp Bristol NHS Fdn Trust, Bristol Biomed Res Ctr, Natl Inst Hlth Res, Bristol, Avon, England; Univ Bristol, Bristol, Avon, England
hcfmusp.author.externalLONDON, Stephanie J.:NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA
hcfmusp.author.externalMAGNUS, Per:Norwegian Inst Publ Hlth, Ctr Fertil & Hlth, Oslo, Norway
hcfmusp.author.externalMCGINNIS, Ralph:Univ Cambridge, Sanger Inst, Cambridge, England
hcfmusp.author.externalNYSTAD, Wenche:Norwegian Inst Publ Hlth, Div Mental & Phys Hlth, Oslo, Norway
hcfmusp.author.externalPAGE, Christian M.:Norwegian Inst Publ Hlth, Div Mental & Phys Hlth, Oslo, Norway; Oslo Univ Hosp, Oslo Ctr Biostat & Epidemiol, Oslo, Norway
hcfmusp.author.externalRIVADENEIRA, Fernando:Erasmus MC, Univ Med Ctr Rotterdam, Generat Study Grp R, Rotterdam, Netherlands; Erasmus MC, Univ Med Ctr Rotterdam, Dept Epidemiol, Rotterdam, Netherlands; Erasmus MC, Univ Med Ctr Rotterdam, Dept Internal Med, Rotterdam, Netherlands
hcfmusp.author.externalSTENE, Lars C.:Norwegian Inst Publ Hlth, Div Mental & Phys Hlth, Oslo, Norway
hcfmusp.author.externalTAPIA, German:Norwegian Inst Publ Hlth, Div Mental & Phys Hlth, Oslo, Norway
hcfmusp.author.externalWILLIAMS, Nicholas:Univ Cambridge, Sanger Inst, Cambridge, England
hcfmusp.author.externalFRASER, Abigail:Univ Bristol, Med Res Council Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England; Univ Bristol Sch Med, Dept Populat Hlth Sci, Bristol, Avon, England; Univ Hosp Bristol NHS Fdn Trust, Bristol Biomed Res Ctr, Natl Inst Hlth Res, Bristol, Avon, England; Univ Bristol, Bristol, Avon, England
hcfmusp.citation.scopus33
hcfmusp.contributor.author-fmusphcCAROLINA BONILLA RICHERO
hcfmusp.description.articlenumberk2167
hcfmusp.description.volume361
hcfmusp.origemWOS
hcfmusp.origem.pubmed29925546
hcfmusp.origem.scopus2-s2.0-85048932986
hcfmusp.origem.wosWOS:000436499500002
hcfmusp.publisher.cityLONDON
hcfmusp.publisher.countryENGLAND
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