In-utero exposure to maternal diabetes and DNA methylation alterations in the Next Generation birth cohort
Notice bibliographique
Résumé
INTRODUCTION: The incidence of type 2 diabetes (T2D) in youth is increasing and in-utero exposure to maternal diabetes is a known risk factor, with higher risk associated with pregestational T2D exposure compared to gestational diabetes mellitus (GDM) exposure. We hypothesize this differential risk is reflected in DNA methylation (DNAm) changes induced by differential timing of in-utero exposure to maternal diabetes, and that exposure to diabetes throughout pregnancy (T2D) compared to exposure later in development (GDM), induces different DNAm signatures and different T2D risk to offspring. This study presents an epigenome-wide investigation of DNAm alterations associated with in-utero exposure to either maternal pregestational T2D or GDM, to determine if the timing of prenatal diabetes exposure differentially alters DNAm. METHODS: We performed an epigenome-wide analysis on cord blood from 99 newborns exposed to pregestational T2D, 70 newborns exposed to GDM, and 41 unexposed to diabetes in-utero from the Next Generation birth cohort. Associations were tested using multiple linear regression models while adjusting for sex, maternal age, BMI, smoking status, gestational age, cord blood cell type proportions and batch effects. RESULTS: We identified 27 differentially methylated sites associated with exposure to GDM, 27 sites associated with exposure to T2D, and 9 common sites associated with exposure to either GDM or T2D (adjusted p value < 0.05 and effect size estimate > 0.01). One site at CLDN15 and two unannotated sites were previously reported as associated with obesity. We also identified 87 differentially methylated regions (DMRs) associated with in-utero exposure to GDM and 69 DMRs associated with in-utero exposure to T2D. We identified 23 DMR sites that were previously associated with obesity, three with T2D and five with in-utero exposure to GDM. Furthermore, we identified six CpG sites in the PTPRN2 gene, a gene previously associated with DNAm differences in blood of youth with T2D from the same population. CONCLUSION: Our findings support that in-utero exposure to maternal diabetes is associated with DNAm alterations in offspring. Moreover, the timing of maternal diabetes in-utero exposure (GDM or T2D) produces overlapping but distinct DNAm patterns, suggesting that the window of exposure to maternal diabetes produces different molecular modifications and may reflect, at least in part, the difference in risk for youth-onset T2D in offspring. We also identified sites in this study that have been previously associated with T2D or obesity, which may serve as potential early-life biomarkers of exposure and/or risk, warranting further investigation in longitudinal studies.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».