Novel epigenetic link between gestational diabetes mellitus and macrosomia

Author:

Joyce Brian T1ORCID,Liu Huikun2,Wang Leishen2,Wang Jun1,Zheng Yinan1,Nannini Drew1,Drong Alex34,Shiau Stephanie5,Li Weiqin2,Leng Junhong2,Shen Yun67,Gao Ru6,Baccarelli Andrea4,Hu Gang6,Hou Lifang1

Affiliation:

1. Center for Global Oncology, Institute for Global Health, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA

2. Tianjin Women’s & Children’s Health Center, Tianjin, China

3. Big Data Institute, University of Oxford, Oxford, UK

4. Department of Environmental Health Science, Mailman School of Public Health, Columbia University, NY, 10032, USA

5. Department of Biostatistics & Epidemiology, Rutgers School of Public Health, Piscataway, NJ, 08854, USA

6. Pennington Biomedical Research Center, Baton Rouge, LA, 70808, USA

7. Department of Endocrinology & Metabolism, Shanghai Jiao Tong University Affiliated Six People’s Hospital, Shanghai, China

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] ).

Funder

National Institute of General Medical Sciences

European Foundation for the Study of Diabetes (EFSD)/Chinese Diabetes Society (CDS)/Lilly programme for Collaborative Research between China and Europe

NORC Center Grant

COBRE Center Grant

Natural Science Foundation of Tianjin, China

National Institute of Diabetes and Digestive and Kidney Diseases

American Heart Association Children's Strategically Focused Research Network

American Heart Association

National Institute of Environmental Health Studies

Publisher

Future Medicine Ltd

Subject

Cancer Research,Genetics

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