DNA methylation signatures of youth-onset type 2 diabetes and exposure to maternal diabetes
| dc.contributor.author | Salama, Ola E. | |
| dc.contributor.author | Hizon, Nikho | |
| dc.contributor.author | Del Vecchio, Melissa | |
| dc.contributor.author | Kolsun, Kurt | |
| dc.contributor.author | Fonseca, Mario A. | |
| dc.contributor.author | Lin, David T. S. | |
| dc.contributor.author | Urtatiz, Oscar | |
| dc.contributor.author | MacIsaac, Julia L. | |
| dc.contributor.author | Kobor, Michael S. | |
| dc.contributor.author | Sellers, Elizabeth A. C. | |
| dc.contributor.author | Dolinsky, Vernon W. | |
| dc.contributor.author | Dart, Allison B. | |
| dc.contributor.author | Jones, Meaghan J. | |
| dc.contributor.author | Wicklow, Brandy A. | |
| dc.date.accessioned | 2024-06-05T16:16:29Z | |
| dc.date.available | 2024-06-05T16:16:29Z | |
| dc.date.issued | 2024-05-13 | |
| dc.date.updated | 2024-06-04T17:48:44Z | |
| dc.description.abstract | Abstract Objective Youth-onset type 2 diabetes (T2D) is physiologically distinct from adult-onset, but it is not clear how the two diseases differ at a molecular level. In utero exposure to maternal type 2 diabetes (T2D) is known to be a specific risk factor for youth-onset T2D. DNA methylation (DNAm) changes associated with T2D but which differ between youth- and adult-onset might delineate the impacts of T2D development at different ages and could also determine the contribution of exposure to in utero diabetes. Methods We performed an epigenome-wide analysis of DNAm on whole blood from 218 youth with T2D and 77 normoglycemic controls from the iCARE (improving renal Complications in Adolescents with type 2 diabetes through REsearch) cohort. Associations were tested using multiple linear regression models while adjusting for maternal diabetes, sex, age, BMI, smoking status, second-hand smoking exposure, cell-type proportions and genetic ancestry. Results We identified 3830 differentially methylated sites associated with youth T2D onset, of which 3794 were moderately (adjusted p-value < 0.05 and effect size estimate > 0.01) associated and 36 were strongly (adjusted p-value < 0.05 and effect size estimate > 0.05) associated. A total of 3725 of these sites were not previously reported in the EWAS Atlas as associated with T2D, adult obesity or youth obesity. Moreover, three CpGs associated with youth-onset T2D in the PFKFB3 gene were also associated with maternal T2D exposure (FDR < 0.05 and effect size > 0.01). This is the first study to link PFKFB3 and T2D in youth. Conclusion Our findings support that T2D in youth has different impacts on DNAm than adult-onset, and suggests that changes in DNAm could provide an important link between in utero exposure to maternal diabetes and the onset of T2D. | |
| dc.identifier.citation | Clinical Epigenetics. 2024 May 13;16(1):65 | |
| dc.identifier.uri | https://doi.org/10.1186/s13148-024-01675-1 | |
| dc.identifier.uri | http://hdl.handle.net/1993/38251 | |
| dc.language.rfc3066 | en | |
| dc.rights | open access | en_US |
| dc.rights.holder | The Author(s) | |
| dc.title | DNA methylation signatures of youth-onset type 2 diabetes and exposure to maternal diabetes | |
| dc.type | Journal Article |