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dc.contributor.authorPetry, Cliveen
dc.contributor.authorSanz Marcos, Nen
dc.contributor.authorPimentel, Gen
dc.contributor.authorHayes, MGen
dc.contributor.authorNodzenski, Men
dc.contributor.authorScholtens, DMen
dc.contributor.authorHughes, Ieuanen
dc.contributor.authorAcerini, Carloen
dc.contributor.authorOng, Kennethen
dc.contributor.authorLowe, WLen
dc.contributor.authorDunger, Daviden
dc.date.accessioned2016-11-29T11:26:10Z
dc.date.available2016-11-29T11:26:10Z
dc.date.issued2016-12-01en
dc.identifier.issn0194-911X
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/261336
dc.description.abstractIn addition to maternal genes and environmental exposures, variation in fetal imprinted genes could also affect maternal blood pressure during pregnancy. Our objective was to test the associations between polymorphic variants in 16 imprinted genes and maternal mean arterial blood pressures in 1160 DNA trios from 2 established birth cohorts (the Cambridge Baby Growth and Wellbeing Studies) and seek replication in 1367 Hyperglycemia and Adverse Pregnancy Outcome Study participants. Significant univariate associations, all independent of fetal sex, were observed in the Cambridge cohorts, including $\textit{FAM99A}$ rs1489945 transmitted from the mother ($\textit{P}$=2×10$^{-4}$), $\textit{DLK1}$ rs10139403 (mother; P=9×10$^{-4}$), $\textit{DLK1}$ rs12147008 (mother; $\textit{P}$=1×10$^{-3}$), $\textit{H19}$ rs217222 (father; $\textit{P}$=1×10$^{-3}$), $\textit{SNRPN}$ rs1453556 (father; $\textit{P}$=1×10$^{-3}$), $\textit{IGF2}$ rs6356 (father; $\textit{P}$=1×10$^{-3}$), and $\textit{NNAT}$ rs6066671 (father; $\textit{P}$=1×10$^{-3}$). In meta-analysis including additional independent Hyperglycemia and Adverse Pregnancy Outcome Study data, the association with maternally transmitted fetal $\textit{DLK1}$ rs10139403 reached genome-wide significance ($\textit{P}$=6.3×10$^{-10}$). With the exception of fetal rs1489945 and rs217222, all of other associations were unidirectional and most were statistically significant. To further explore the significance of these relationships, we developed an allele score based on the univariate findings. The score was strongly associated with maternal blood pressure at 31 weeks ($\textit{P}$=4.1×10$^{-8}$; adjusted $\textit{r}$$^{2}$=5.6%) and 37 weeks of pregnancy ($\textit{P}$=1.1×10$^{-4}$; $\textit{r}$$^{2}$=3.6%), and during the last 2 weeks before parturition ($\textit{P}$=1.1×10$^{-10}$; $\textit{r}$$^{2}$=8.7%). It was also associated with gestational hypertension (odds ratio, 1.54 [range, 1.14-2.09] per allele; $\textit{P}$=0.005; 45 cases and 549 controls). These data support the concept that fetal imprinted genes are related to the development of gestational hypertension.
dc.description.sponsorshipThe genotyping part of the Cambridge Baby Growth Study was funded by the Evelyn Trust (EW9035322), Diabetes U.K. (11/0004241) and the Wellbeing of Women (the Royal College of Obstetricians and Gynaecologists, U.K.) (RG1644). Other core funding has come from the Medical Research Council (7500001180); European Union Framework 5 (QLK4-1999-01422); the Mothercare Charitable Foundation (RG54608); Newlife Foundation for Disabled Children (07/20) and the World Cancer Research Fund International (2004/03). In addition there has been support from National Institute for Health Research Cambridge Biomedical Research Centre. The HAPO Study was supported by NIH grants HD-34242, HD-34243, HG-004415, and CA-141688, Institutes of Health Research–INMD (Funding Reference Number 110791), and by the American Diabetes Association.
dc.languageENGen
dc.language.isoenen
dc.publisherAmerican Heart Association
dc.rightsAttribution-NonCommercial 4.0 Internationalen
dc.rightsAttribution-NonCommercial 4.0 Internationalen
dc.rightsAttribution-NonCommercial 4.0 Internationalen
dc.rightsAttribution-NonCommercial 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/en
dc.subjectblood pressureen
dc.subjecthypertensionen
dc.subjectpregnancy-induceden
dc.subjectmeta-analysisen
dc.subjectplacentaen
dc.subjectpreeclampsiaen
dc.titleAssociations Between Fetal Imprinted Genes and Maternal Blood Pressure in Pregnancyen
dc.typeArticle
prism.endingPage1466
prism.issueIdentifier6en
prism.publicationDate2016en
prism.publicationNameHypertensionen
prism.startingPage1459
prism.volume68en
dc.identifier.doi10.17863/CAM.6503
dcterms.dateAccepted2016-09-29en
rioxxterms.versionofrecord10.1161/HYPERTENSIONAHA.116.08261en
rioxxterms.versionAMen
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by-nc/4.0/en
rioxxterms.licenseref.startdate2016-12-01en
dc.contributor.orcidPetry, Clive [0000-0002-6642-9825]
dc.contributor.orcidAcerini, Carlo [0000-0003-2121-5871]
dc.contributor.orcidOng, Kenneth [0000-0003-4689-7530]
dc.contributor.orcidDunger, David [0000-0002-2566-9304]
dc.identifier.eissn1524-4563
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idWellbeing of Women (RG1644)
pubs.funder-project-idNational Institute for Health Research ()
pubs.funder-project-idNational Institute for Health Research (NIHR) (via West Anglia Comprehensive Local Research Network (CLRN)) (UKCRN 11822)
pubs.funder-project-idMRC Epidemiology Unit (7500001180)
pubs.funder-project-idMothercare Charitable Foundation (unknown)
pubs.funder-project-idMRC (MC_UU_12015/2)
pubs.funder-project-idMRC (G0600717B)
pubs.funder-project-idDiabetes UK (DUK-11/0004241)
pubs.funder-project-idMedical Research Council (MC_U106179472)
cam.issuedOnline2016-10-24en
rioxxterms.freetoread.startdate2017-04-24


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Attribution-NonCommercial 4.0 International
Except where otherwise noted, this item's licence is described as Attribution-NonCommercial 4.0 International