Novel epigenetic link between gestational diabetes mellitus and macrosomia

Abstract

Background & objectives: Examine maternal gestational diabetes mellitus (GDM), macrosomia and DNA methylation in candidate genes IGF1, IGF2, H19, ARHGRF11, MEST, NR3C1, ADIPOQ and RETN. Materials & methods: A total of 1145 children (572 GDM cases and 573 controls) from the Tianjin GDM study, including 177 with macrosomia, had blood DNA collection at median age 5.9 (range: 3.1-10.0). We used logistic regression to screen for associations with GDM and model macrosomia on 37 CpGs, and performed mediation analysis. Results: One CpG was associated with macrosomia at false discovery rate (FDR) <0.05 (cg14428359 in MEST); two (cg19466922 in MEST and cg26263166 in IGF2) were associated at p < 0.05 but mediated 26 and 13%, respectively. Conclusion:MEST and IGF2 were previously identified for potential involvement in fetal growth and development (Trial Registration number: NCT01554358 [ClinicalTrials.gov]).

Keywords: epigenetic epidemiology; epigenetics; macrosomia; metabolic diseases; pediatrics.

Conflict of interest statement

Financial & competing interests disclosure

This study was supported by grants from the European Foundation for the Study of Diabetes (EFSD)/Chinese Diabetes Society (CDS)/Lilly programme for Collaborative Research between China and Europe, and the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK100790). This project also used core facilities supported by the NORC Center Grant P30 DK072476, and the COBRE Center Grant P30 GM118430. G Hu was partly supported by the grant from the National Institute of General Medical Sciences (U54GM104940). A Baccarelli was partially supported by a grant from the National Institute of Environmental Health Studies (P30ES009089). L Hou was partially supported by the American Heart Association Children’s Strategically Focused Research Network. BT Joyce was partially supported by an American Heart Association Career Development Award (Grant number 19CDA34630050). H Liu was supported by the Natural Science Foundation of Tianjin, China (19JCYBJC28000). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Figures

Figure 1.. Results of mediation analysis of three CpGs associated with macrosomia and GDM at p 

All models adjusted for maternal height, age, smoking status, passive smoking exposure, prepregnancy BMI, pregnancy weight gain, parity, pregnancy hypertension, child sex and gestational age at delivery, child age and weight for age z-score at methylation measurement, blood cell type proportions and ten principal components representing processing batch effects (>90% of variance). GDM: Gestational diabetes mellitus.