Epigenome-wide meta-analysis of prenatal vitamin D insufficiency and cord blood DNA methylation
Elizabeth W. Diemer,
Johanna Tuhkanen,
Sara Sammallahti,
Kati Heinonen,
Alexander Neumann,
Sonia L. Robinson,
Matthew Suderman,
Jianping Jin,
Christian M. Page,
Ruby Fore,
Sheryl L. Rifas-Shiman,
Emily Oken,
Patrice Perron,
Luigi Bouchard,
Marie France Hivert,
Katri Räikköne,
Jari Lahti,
Edwina H. Yeung,
Weihua Guan,
Sunni L. Mumford,
Maria C. Magnus,
Siri Håberg,
Wenche Nystad,
Christine L. Parr,
Stephanie J. London,
Janine F. Felix,
Henning Tiemeier
Affiliations
Elizabeth W. Diemer
Department of Child and Adolescent Psychiatry, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
Johanna Tuhkanen
Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland
Sara Sammallahti
Department of Child and Adolescent Psychiatry, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
Kati Heinonen
Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland
Alexander Neumann
Department of Child and Adolescent Psychiatry, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
Sonia L. Robinson
Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA
Matthew Suderman
MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
Jianping Jin
Westat, Durham, NC, USA
Christian M. Page
Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway
Ruby Fore
Department of Population Medicine, Harvard Medical School, Harvard Pilgrim Health Care Institute, Boston, MA, USA
Sheryl L. Rifas-Shiman
Department of Population Medicine, Harvard Medical School, Harvard Pilgrim Health Care Institute, Boston, MA, USA
Emily Oken
Department of Population Medicine, Harvard Medical School, Harvard Pilgrim Health Care Institute, Boston, MA, USA
Patrice Perron
Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, QC, Canada
Luigi Bouchard
Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, QC, Canada
Marie France Hivert
Department of Population Medicine, Harvard Medical School, Harvard Pilgrim Health Care Institute, Boston, MA, USA
Katri Räikköne
Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland
Jari Lahti
Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland
Edwina H. Yeung
Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA
Weihua Guan
Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, USA
Sunni L. Mumford
Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA
Maria C. Magnus
Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway
Siri Håberg
Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway
Wenche Nystad
Department of Chronic Diseases and Ageing, Norwegian Institute of Public Health, Oslo, Norway
Christine L. Parr
Department of Chronic Diseases and Ageing, Norwegian Institute of Public Health, Oslo, Norway
Stephanie J. London
Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC, USA
Janine F. Felix
Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
Henning Tiemeier
Department of Child and Adolescent Psychiatry, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
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: see text] 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.
