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DNA methylation risk score for type 2 diabetes is associated with gestational diabetes

Title: DNA methylation risk score for type 2 diabetes is associated with gestational diabetes
Authors: Linares-Pineda, Teresa M.; Fragoso-Bargas, Nicolas; Picón, María José; Molina-Vega, Maria; Jenum, Anne Karen; Sletner, Line; Lee-Ødegård, Sindre; Opsahl, Julia O.; Moen, Gunn Helen; Qvigstad, Elisabeth; Prasad, Rashmi B.; Birkeland, Kåre I.; Morcillo, Sonsoles; Sommer, Christine
Contributors: Institute for Molecular Medicine Finland
Publisher Information: BioMed Central
Publication Year: 2025
Collection: Helsingfors Universitet: HELDA – Helsingin yliopiston digitaalinen arkisto
Subject Terms: DNA epigenetics; Epigenetics; Gestational diabetes; Methylation risk score; Type 2 diabetes; Genetics; developmental biology; physiology
Description: Background: Gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM) share many pathophysiological factors including genetics, but whether epigenetic marks are shared is unknown. We aimed to test whether a DNA methylation risk score (MRS) for T2DM was associated with GDM across ancestry and GDM criteria. Methods: In two independent pregnancy cohorts, EPIPREG (n = 480) and EPIDG (n = 32), DNA methylation in peripheral blood leukocytes was measured at a gestational age of 28 ± 2. We constructed an MRS in EPIPREG and EPIDG based on CpG hits from a published epigenome-wide association study (EWAS) of T2DM. Results: With mixed models logistic regression of EPIPREG and EPIDG, MRS for T2DM was associated with GDM: odd ratio (OR)[95% CI]: 1.3 [1.1–1.8], P = 0.002 for the unadjusted model, and 1.4 [1.1–1.7], P = 0.00014 for a model adjusted by age, pre-pregnant BMI, family history of diabetes and smoking status. Also, we found 6 CpGs through a meta-analysis (cg14020176, cg22650271, cg14870271, cg27243685, cg06378491, cg25130381) associated with GDM, and some of their methylation quantitative loci (mQTLs) were related to T2DM and GDM. Conclusion: For the first time, we show that DNA methylation marks for T2DM are also associated with GDM, suggesting shared epigenetic mechanisms between GDM and T2DM. ; Peer reviewed
Document Type: article in journal/newspaper
File Description: application/pdf
Language: English
Relation: EPIPREG is supported by the South Eastern Norway Regional Health Authority (grant number: 2019092), and the Norwegian Diabetes Association (grant number: N/A). GH-M. is the recipient of an Australian Research Council Discovery Early Career Award (Project number: DE220101226) funded by the Australian Government and supported by the Research Council of Norway (Project grant: 325640). JO-O is supported by the Norwegian Research Council (Medical Student Research Program, grant 271555/F20). EPIDG was funded by the Juan Rodés program from “Instituto de Salud Carlos III” (JR20-00040 to MM-V), PFIS program (FI19/00178 to TML-P), and the Nicolas Monardes Program from the “Servicio Andaluz de Salud, Junta de Andalucía”, Spain (RC-0008-2021 to SM). In addition, this study was supported by the research grants from the ISCIII (PI18/01175, PI21/01864) and from “Servicio Andaluz de Salud”, Junta de Andalucía (PI-0283-2018, PI-0419-2019). This study has been co-funded by FEDER funds (“A way to make Europe”).; The authors thank the women who participated in the STORK Groruddalen study and EPIDG study.; https://hdl.handle.net/10138/592571; 85185131280; 001161999400002
Availability: https://hdl.handle.net/10138/592571
Rights: cc_by ; info:eu-repo/semantics/openAccess ; openAccess
Accession Number: edsbas.A3B1F25E
Database: BASE