Leanne K Küpers1,2, Sílvia Fernández-Barrés3,4,5, Giulia Mancano6,7, Laura Johnson6,8, Raffael Ott9,10, Jesus Vioque5,11,12, Marco Colombo13, Kathrin Landgraf13, Elmar W Tobi14, Antje Körner13, Romy Gaillard1,2, Jeanne H M de Vries15, Vincent W V Jaddoe1,2, Martine Vrijheid3,4,5, Gemma C Sharp6,7, Janine F Felix1,2. 1. The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands. 2. Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands. 3. ISGlobal, Barcelona Institute for Global Health, Barcelona, Spain. 4. Universitat Pompeu Fabra (UPF), Barcelona, Spain. 5. CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. 6. MRC Integrative Epidemiology Unit, University of Bristol, Bristol, U.K. 7. Bristol Medical School Population Health Sciences, University of Bristol, Bristol, U.K. 8. Centre for Exercise, Nutrition and Health Sciences, University of Bristol, Bristol, U.K. 9. Institute of Diabetes Research, Helmholtz Zentrum München, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Neuherberg, Germany. 10. Forschergruppe Diabetes e.V., Neuherberg, Germany. 11. Universidad Miguel Hernandez, Sant Joan d'Alacant, Alicante, Spain. 12. Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL-UMH), Alicante, Spain. 13. University of Leipzig, Medical Faculty, University Hospital for Children and Adolescents, Center for Pediatric Research, Leipzig, Germany. 14. Periconceptional Epidemiology, Division of Obstetrics and Prenatal Medicine, Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands. 15. Division of Human Nutrition and Health, Wageningen University and Research, the Netherlands.
Abstract
OBJECTIVE: Suboptimal nutrition in pregnancy is associated with worse offspring cardiometabolic health. DNA methylation may be an underlying mechanism. We meta-analyzed epigenome-wide association studies (EWAS) of maternal dietary glycemic index and load with cord blood DNA methylation. RESEARCH DESIGN AND METHODS: We calculated maternal glycemic index and load from food frequency questionnaires and ran EWAS on cord blood DNA methylation in 2,003 mother-offspring pairs from three cohorts. Analyses were additionally stratified by maternal BMI categories. We looked-up the findings in EWAS of maternal glycemic traits and BMI as well as in EWAS of birth weight and child BMI. We examined associations with gene expression in child blood in the online Human Early Life Exposome eQTM catalog and in 223 adipose tissue samples. RESULTS: Maternal glycemic index and load were associated with cord blood DNA methylation at 41 cytosine-phosphate-guanine sites (CpGs, P < 1.17 × 10-7), mostly in mothers with overweight/obesity. We did not observe overlap with CpGs associated with maternal glycemic traits, BMI, or child birth weight or BMI. Only DNA methylation at cg24458009 and cg23347399 was associated with expression of PCED1B and PCDHG, respectively, in child blood, and DNA methylation at cg27193519 was associated with expression of TFAP4, ZNF500, PPL, and ANKS3 in child subcutaneous adipose tissue. CONCLUSIONS: We observed multiple associations of maternal glycemic index and load during pregnancy with cord blood DNA methylation, mostly in mothers with overweight/obesity; some of these CpGs were associated with gene expression. Additional studies are required to further explore functionality, uncover causality, and study pathways to offspring health.
OBJECTIVE: Suboptimal nutrition in pregnancy is associated with worse offspring cardiometabolic health. DNA methylation may be an underlying mechanism. We meta-analyzed epigenome-wide association studies (EWAS) of maternal dietary glycemic index and load with cord blood DNA methylation. RESEARCH DESIGN AND METHODS: We calculated maternal glycemic index and load from food frequency questionnaires and ran EWAS on cord blood DNA methylation in 2,003 mother-offspring pairs from three cohorts. Analyses were additionally stratified by maternal BMI categories. We looked-up the findings in EWAS of maternal glycemic traits and BMI as well as in EWAS of birth weight and child BMI. We examined associations with gene expression in child blood in the online Human Early Life Exposome eQTM catalog and in 223 adipose tissue samples. RESULTS: Maternal glycemic index and load were associated with cord blood DNA methylation at 41 cytosine-phosphate-guanine sites (CpGs, P < 1.17 × 10-7), mostly in mothers with overweight/obesity. We did not observe overlap with CpGs associated with maternal glycemic traits, BMI, or child birth weight or BMI. Only DNA methylation at cg24458009 and cg23347399 was associated with expression of PCED1B and PCDHG, respectively, in child blood, and DNA methylation at cg27193519 was associated with expression of TFAP4, ZNF500, PPL, and ANKS3 in child subcutaneous adipose tissue. CONCLUSIONS: We observed multiple associations of maternal glycemic index and load during pregnancy with cord blood DNA methylation, mostly in mothers with overweight/obesity; some of these CpGs were associated with gene expression. Additional studies are required to further explore functionality, uncover causality, and study pathways to offspring health.
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