6533b82dfe1ef96bd1290965

RESEARCH PRODUCT

Association of maternal prenatal smoking GFI1-locus and cardio-metabolic phenotypes in 18,212 adults

Petri WiklundPetri WiklundPetri WiklundMelanie WaldenbergerLili MilaniLili MilaniWei ChenAndré G. UitterlindenHans J. GrabePim Van Der HarstShengxu LiPashupati P. MishraJohn C. ChambersRae-chi HuangJaspal S. KoonerGiovanni CugliariLawrence J. BeilinJoyce B. J. Van MeursMika KähönenRory P. WilsonPhillip E. MeltonPhillip E. MeltonP. Eline SlagboomBenjamin LehneMatthias NauckSimonetta GuarreraSylvain SebertSylvain SebertGiuseppe MatulloMatthias WielscherWeihua ZhangWeihua ZhangTao ZhangTao ZhangYan ZhangMikko HurmeNiek De KleinHermann BrennerHermann BrennerMarjo-riitta JärvelinKrista FischerAnnette PetersSilva KaselaTrevor A. MoriTaulant MukaTerho LehtimäkiOscar H. FrancoLeonard H. Van Den BergPooja R. MandaviyaToby AndrewMatthew SudermanMarie LohMarie LohMarie LohNiek VerweijLude FrankeVille KarhunenPriyanka ParmarWolfgang RathmannAlexander TeumerJana NanoSonja KunzeEstelle LowryDenise AndersonChristian GiegerPhilippe FroguelPhilippe FroguelDorret I. BoomsmaJan H. VeldinkMarleen M.j. Van GreevenbroekCaroline L ReltonSalvatore PanicoBastiaan T. HeijmansAmélie BonnefondAmélie BonnefondStephan B. FelixOlli T. RaitakariOlli T. RaitakariBen SchöttkerBen Schöttker

subject

Genetics and Molecular Biology (all)MaleNetherlands Twin Register (NTR)0301 basic medicineResearch paperGFI1 protein humanGFI1-locusraskausResearch & Experimental Medicinecardio-metabolic phenotypesBiochemistryEpigenesis GeneticGLOBAL Meth QTL Consortium0302 clinical medicinePregnancySmoke030212 general & internal medicinematernal prenatal smokingDNA METHYLATIONmedia_commonRISK2. Zero hungereducation.field_of_studySmokingta3142General MedicineMiddle Agedgenetics [Transcription Factors]3. Good healthDNA-Binding ProteinsPhenotypeMedicine Research & ExperimentalCARDIOVASCULAR-DISEASEepigenetiikkaPopulation SurveillancePrenatal Exposure Delayed EffectsDNA methylation/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_beingFemaleDisease SusceptibilityBIOS ConsortiumMedical GeneticsLife Sciences & BiomedicineAdultmedicine.medical_specialtyOffspringBirth weightPopulationMothersgenetics [DNA-Binding Proteins]ta3111MethylationGeneral Biochemistry Genetics and Molecular BiologyDIET03 medical and health sciencesMedicine General & InternalSDG 3 - Good Health and Well-beingtupakointiGeneral & Internal MedicineInternal medicine/dk/atira/pure/keywords/cohort_studies/netherlands_twin_register_ntr_medicinemedia_common.cataloged_instanceHumansddc:610adverse effects [Maternal Exposure]EXPOSUREEpigeneticsEuropean unioneducationMedicinsk genetikEPIGENOME-WIDE ASSOCIATIONPregnancyBiochemistry Genetics and Molecular Biology (all)Science & Technologybusiness.industryadverse effects [Smoking]DNA Methylationta3121medicine.diseaseBIRTH-WEIGHT030104 developmental biologyEndocrinologyGenetic Locisydän- ja verisuonitauditCpG IslandsCIGARETTE-SMOKINGCESSATIONEnergy Metabolismmetabolism [Myocardium]businessBody mass indexBiomarkersTranscription Factors

description

Background: DNA methylation at the GFI1-locus has been repeatedly associated with exposure to smoking from the foetal period onwards. We explored whether DNA methylation may be a mechanism that links exposure to maternal prenatal smoking with offspring's adult cardio-metabolic health.Methods: We meta-analysed the association between DNA methylation at GFI1-locus with maternal prenatal smoking, adult own smoking, and cardio-metabolic phenotypes in 22 population-based studies from Europe, Australia, and USA (n= 18,212). DNA methylation at the GFI1-locus was measured in whole-blood. Multivariable regression models were fitted to examine its association with exposure to prenatal and own adult smoking. DNA methylation levels were analysed in relation to body mass index (BMI), waist circumference (WC), fasting glucose (FG), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), diastolic, and systolic blood pressure (BP).Findings: Lower DNA methylation at three out of eight GFI1-CpGs was associated with exposure to maternal prenatal smoking, whereas, all eight CpGs were associated with adult own smoking. Lower DNA methylation at cg14179389, the strongest maternal prenatal smoking locus, was associated with increased WC and BP when adjusted for sex, age, and adult smoking with Bonferroni-corrected P <0.012. In contrast, lower DNA methylation at cg09935388, the strongest adult own smoking locus, was associated with decreased BMI, WC, and BP (adjusted 1 x 10(-7) <P <0.01). Similarly, lower DNA methylation at cg12876356, cg18316974, cg09662411, and cg18146737 was associated with decreased BMI and WC (5 x 10(-8) <P <0.001). Lower DNA methylation at all the CpGs was consistently associated with higher TG levels.Interpretation: Epigenetic changes at the GFI1 were linked to smoking exposure in-utero/in-adulthood and robustly associated with cardio-metabolic risk factors. Fund: European Union's Horizon 2020 research and innovation programme under grant agreement no. 633595 DynaHEALTH. (c) 2018 The Authors. Published by Elsevier B.V.

yearjournalcountryeditionlanguage
2018-12-01EBioMedicine
10.1016/j.ebiom.2018.10.066http://dx.doi.org/10.1016/j.ebiom.2018.10.066