DNA methylation signatures of youth-onset type 2 diabetes and exposure to maternal diabetes

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dc.contributor.authorSalama, Ola E.
dc.contributor.authorHizon, Nikho
dc.contributor.authorDel Vecchio, Melissa
dc.contributor.authorKolsun, Kurt
dc.contributor.authorFonseca, Mario A.
dc.contributor.authorLin, David T. S.
dc.contributor.authorUrtatiz, Oscar
dc.contributor.authorMacIsaac, Julia L.
dc.contributor.authorKobor, Michael S.
dc.contributor.authorSellers, Elizabeth A. C.
dc.contributor.authorDolinsky, Vernon W.
dc.contributor.authorDart, Allison B.
dc.contributor.authorJones, Meaghan J.
dc.contributor.authorWicklow, Brandy A.
dc.date.accessioned2024-06-05T16:16:29Z
dc.date.available2024-06-05T16:16:29Z
dc.date.issued2024-05-13
dc.date.updated2024-06-04T17:48:44Z
dc.description.abstractObjective 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.citationClinical Epigenetics. 2024 May 13;16(1):65
dc.identifier.doi10.1186/s13148-024-01675-1
dc.identifier.urihttp://hdl.handle.net/1993/38251
dc.language.isoeng
dc.language.rfc3066en
dc.publisherBMC
dc.rightsopen accessen_US
dc.rights.holderThe Author(s)
dc.subjectDiabetes in youth
dc.subjectDNA methylation
dc.subjectType 2 diabetes
dc.subjectEpigenetics
dc.subjectIn utero programing
dc.titleDNA methylation signatures of youth-onset type 2 diabetes and exposure to maternal diabetes
dc.typeJournal Article
local.author.affiliationRady Faculty of Health Sciences::Max Rady College of Medicine::Department of Biochemistry and Medical Genetics
oaire.citation.issue65
oaire.citation.titleClinical Epigenetics
oaire.citation.volume16
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