| Description: |
Low maternal vitamin D concentrations during pregnancy have been associated with a range of offspring health outcomes. DNA methylation is one mechanism by which the maternal vitamin D status during pregnancy could impact offspring’s health in later life. We aimed to evaluate whether maternal vitamin D insufficiency during pregnancy was conditionally associated with DNA methylation in the offspring cord blood. Maternal vitamin D insufficiency (plasma 25-hydroxy vitamin D (Formula presented.) 75 nmol/L) during pregnancy and offspring cord blood DNA methylation, assessed using Illumina Infinium 450k or Illumina EPIC Beadchip, was collected for 3738 mother–child pairs in 7 cohorts as part of the Pregnancy and Childhood Epigenetics (PACE) consortium. Associations between maternal vitamin D and offspring DNA methylation, adjusted for fetal sex, maternal smoking, maternal age, maternal pre-pregnancy or early pregnancy BMI, maternal education, gestational age at measurement of 25(OH)D, parity, and cell type composition, were estimated using robust linear regression in each cohort, and a fixed-effects meta-analysis was conducted. The prevalence of vitamin D insufficiency ranged from 44.3% to 78.5% across cohorts. Across 364,678 CpG sites, none were associated with maternal vitamin D insufficiency at an epigenome-wide significant level after correcting for multiple testing using Bonferroni correction or a less conservative Benjamini–Hochberg False Discovery Rate approach (FDR, p > 0.05). In this epigenome-wide association study, we did not find convincing evidence of a conditional association of vitamin D insufficiency with offspring DNA methylation at any measured CpG site. ; Peer reviewed |
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Elizabeth Diemer is supported by an innovation program under the Marie Sklowdowska-Curie grant agreement no. 721567. The work of Henning Tiemeier was supported by a NWO-VICI grant (NWO-ZonMW: 016.VICI.170.200). This work was supported by the Academy of Finland (grant number 1323910). The work of Edwina H Yeung, Sonia L Robinson, and Sunni L Mumford was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (NIH), contract numbers HHSN267200603423, HHSN267200603424, HHSN267200603426, and HHSN275201300023I-HHSN2750008. The UK Medical Research Council and Wellcome (grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors and Matthew Suderman will serve as a guarantor for the contents of this paper. This work was partly supported by the Research Council of Norway through its Centres of Excellence funding scheme, project number 262700. The work of Sara Sammallahti was supported by the EU Marie Sklodowska-Curie LeadingFellows COFUND Programme and by the Orion Research Fund. The general design of the Generation R Study is made possible by financial support from Erasmus MC, University Medical Center Rotterdam, Erasmus University Rotterdam; the Netherlands Organization for Health Research and Development; and the Ministry of Health, Welfare and Sport. The EWAS data were funded by a grant from the Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) Netherlands Consortium for Healthy Aging (NCHA; project nr. 050-060-810); by funds from the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC; and by a grant from the National Institute of Child and Human Development (R01HD068437). This project received funding from the European Union\u2019s Horizon 2020 research and innovation programme (733206, LIFECYCLE; 874739, LongITools; 824989, EUCAN-Connect) and from the European Joint Programming Initiative \u201CA Healthy Diet for a Healthy Life\u201D (JPI HDHL, NutriPROGRAM project, ZonMw, the Netherlands (no. 529051022) and the PREcisE project ZonMw, the Netherlands (no. 529051023)). The Norwegian Mother, Father and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research. We are grateful to all the participating families in Norway who take part in this on-going cohort study. The work was supported by the\u00A0HORIZON EUROPE Marie Sklodowska-Curie Actions [721567]; European Union Horizon 2020 [874739]; European Union Horizon 2020 [824989]; European Union Horizon 2020 [733206]; Intramural Research Program [HHSN2752013000231-HHSN2750008]; Intramural Research Program [HHSN267200603426]; Intramural Research Program [HHSN267200603423]; Intramural Research Program [HHSN26700603424]; National Institute of Child Health and Human Development [R01HD068437]; Nederlandse Organisatie voor Wetenschappelijk Onderzoek [050-060-810]; Nederlandse Organisatie voor Wetenschappelijk Onderzoek [016.VICI.170.200]; Norges Forskningsr\u00E5d [2622700]; Orionin Tutkimuss\u00E4\u00E4ti\u00F6; Marie Sklodowska-Cure COFUND Action [LEaDing Fellows 707404]; Research Council of Finland [1323910]; UKRI Medical Research Council; Wellcome Trust [217065Z/19/Z]; ZonMw [529051022]; ZonMw [529051023]. Elizabeth Diemer is supported by an innovation program under the Marie Sklowdowska-Curie grant agreement no. 721567. The work of Henning Tiemeier was supported by a NWO-VICI grant (NWO-ZonMW: 016.VICI.170.200). This work was supported by the Academy of Finland (grant number 1323910). The work of Edwina H Yeung, Sonia L Robinson, and Sunni L Mumford was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (NIH), contract numbers HHSN267200603423, HHSN267200603424, HHSN267200603426, and HHSN275201300023I-HHSN2750008. The UK Medical Research Council and Wellcome (grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors and Matthew Suderman will serve as a guarantor for the contents of this paper. This work was partly supported by the Research Council of Norway through its Centres of Excellence funding scheme, project number 262700. The work of Sara Sammallahti was supported by the EU Marie Sklodowska-Curie LeadingFellows COFUND Programme and by the Orion Research Fund. We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, and nurses. The Generation R Study is conducted by Erasmus MC, University Medical Center Rotterdam, in close collaboration with the School of Law and Faculty of Social Sciences of the Erasmus University Rotterdam, the Municipal Health Service Rotterdam area, Rotterdam, the Rotterdam Homecare Foundation, Rotterdam and the Stichting Trombosedienst & Artsenlaboratorium Rijnmond (STAR-MDC), Rotterdam. We gratefully acknowledge the contribution of children and parents, general practitioners, hospitals, midwives, and pharmacies in Rotterdam. The study protocol was approved by the Medical Ethical Committee of the Erasmus Medical Centre, Rotterdam. Written informed consent was obtained from all participants. The generation and management of the Illumina 450K methylation array data (EWAS data) for the Generation R Study were executed by the Human Genotyping Facility of the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, the Netherlands. We thank Mr. Michael Verbiest, Ms. Mila Jhamai, Ms. Sarah Higgins, Mr. Marijn Verkerk, and Dr. Lisette Stolk for their help in creating the EWAS database. We thank Dr. A. Teumer for his work on the quality control and normalization scripts. The general design of the Generation R Study is made possible by financial support from Erasmus MC, University Medical Center Rotterdam, Erasmus University Rotterdam; the Netherlands Organization for Health Research and Development; and the Ministry of Health, Welfare and Sport. The EWAS data were funded by a grant from the Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) Netherlands Consortium for Healthy Aging (NCHA; project nr. 050-060-810); by funds from the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC; and by a grant from the National Institute of Child and Human Development (R01HD068437). This project received funding from the European Union\u2019s Horizon 2020 research and innovation programme (733206, LIFECYCLE; 874739, LongITools; 824989, EUCAN-Connect) and from the European Joint Programming Initiative \u201CA Healthy Diet for a Healthy Life\u201D (JPI HDHL, NutriPROGRAM project, ZonMw, the Netherlands (no. 529051022) and the PREcisE project ZonMw, the Netherlands (no. 529051023)). Gen3G was supported by Fonds de recherche du Qu\u00E9bec \u2013 Sant\u00E9 (FRQS) operating grant (to M-FH, grant no. 20697); a Canadian Institute of Health Research (CIHR) operating grant (to M-FH, grant no. MOP 115071; to LB, #PJT-152989); and a Diab\u00E8te Qu\u00E9bec grant (to PP). The DNA methylation analyses were supported by the American Diabetes Association (ADA) Pathways To Stop Diabetes Accelerator Award (#1-15-ACE-26). We thank Catherine Allard for her analytic support on this project. Project Viva was funded by the United States National Institutes of Health Grant (R01HD034568). We thank Catherine Briggs for her analytic support on this project.; https://hdl.handle.net/10138/595120; 85206834641; 001337705200001 |