Abstract
OBJECTIVE Suboptimal nutrition in pregnancy is associated with worse offspring cardiometa-bolic health. DNA methylation may be an underlying mechanism. We meta-ana-lyzed 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 question-naires 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,andANKS3 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 over-weight/obesity; some of these CpGs were associated with gene expression. Addi-tional studies are required to further explore functionality, uncover causality, and study pathways to offspring health.
| Original language | English |
|---|---|
| Pages (from-to) | 1822-1832 |
| Number of pages | 11 |
| Journal | Diabetes Care |
| Volume | 45 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - 1 Aug 2022 |
Bibliographical note
Funding Information:Acknowledgments. Cohort-specific acknowledgments are stated in the Supplementary Material. Funding. This work was funded by the Joint Programming Initiative – A Healthy Diet for a Healthy Life to the NutriPROGRAM consortium: ZonMW, the Netherlands (529051022), MRC, U.K. (MR/S036520/1), and Instituto de Salud Carlos III, Spain (AC18/00006), and the PREcisE consortium: ZonMW, the Netherlands (529051023), German Federal Ministry of Education and Research, Germany (FKZ 01EA1905). Information regarding funding for the contributing cohorts and individual authors can be found in the Supplementary Material. Duality of Interest. No potential conflicts of interest relevant to this article were reported. Author Contributions. L.K.K. and S.F.-B. performed the meta-analysis. L.K.K., S.F.-B., G.M., L.J., R.O., J.V., M.C., K.L., E.W.T., A.K., R.G., J.H.M.d.V., V.W.V.J., M.V., G.C.S., and J.F.F. interpreted the data. L.K.K., S.F.B., G.M., L.J., R.O., J.V., M.C., K.L., E.W.T., A.K., R.G., J.H.M.d.V., V.W.V.J., M.V., G.C.S., and J.F.F. contributed to critical revision for important intellectual content. L.K.K., S.F.B., G.M., L.J., R.O., J.V., M.C., K.L., E.W.T., A.K., R.G., J.H.M.d.V., V.W.V.J., M.V., G.C.S., and J.F.F. gave final approval of the version to be published. L.K.K., S.F.B., G.M., L.J., J.V., K.L., and M.C. conducted cohort-specific analyses. L.K.K. and J.F.F. designed the research. L.K.K. and J.F.F. drafted the manuscript. A.K., R.G., V.W.V.J., M.V., G.C.S., and J.F.F. acquired data. L.K.K. and J.F.F. are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
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