Aim: Myotonic dystrophy type 1 (DM1) is caused by an unstable trinucleotide (CTG) expansion at the DMPK gene locus. Cognitive dysfunctions are often observed in the condition. We investigated the association between DMPK blood DNA methylation (DNAm) and cognitive functions in DM1, considering expansion length and variant repeats (VRs). Method: Data were obtained from 115 adult-onset DM1 patients. Molecular analyses consisted of pyrosequencing, small pool PCR and Southern blot hybridization. Cognitive functions were assessed by validated neuropsychological tests. Results: For patients without VRs (n = 103), blood DNAm at baseline independently contributed to predict cognitive functions 9 years later. Patients with VRs (n = 12) had different DNAm and cognitive profiles. Conclusion: DNAm allows to better understand DM1-related cognitive dysfunction etiology.

Changes in fetal DNA methylation (DNAm) of the leptin (LEP) gene have been associated with exposure to maternal hyperglycemia, but their links with childhood obesity risk are still unclear. We investigated the association between maternal hyperglycemia, placental LEP DNAm (25 5′-C-phosphate-G-3′ (CpG) sites), neonatal leptinemia, and adiposity (i.e., BMI and skinfold thickness (ST) (subscapular (SS) + triceps (TR) skinfold measures, and the ratio of SS:TR) at 3-years-old, in 259 mother–child dyads, from Gen3G birth cohort. We conducted multivariate linear analyses adjusted for gestational age at birth, sex of the child, age at follow-up, and cellular heterogeneity. We assessed the causal role of DNAm in the association between maternal glycemia and childhood outcomes, using mediation analysis. We found three CpGs associated with neonatal leptinemia (p ≤ 0.002). Of these, cg05136031 and cg15758240 were also associated with BMI (β = −2.69, p = 0.05) and fat distribution (β = −0.581, p = 0.05) at 3-years-old, respectively. Maternal glycemia was associated with DNAm at cg15758240 (β = −0.01, p = 0.04) and neonatal leptinemia (β = 0.19, p = 0.004). DNAm levels at cg15758240 mediates 0.8% of the association between maternal glycemia and neonatal leptinemia (p < 0.001). Our results support that DNAm regulation of the leptin pathway in response to maternal glycemia might be involved in programming adiposity in childhood.

Background Adolescence is a critical period for the development of eating disorders, but data is lacking on the heterogeneity of their evolution during that time-period. Group-based trajectories can be used to understand how eating disorders emerge and evolve over time. The aim of this study was to identify groups of individuals with distinct levels of eating disorder symptoms between 12 and 20 years and the onset of different types of symptoms. We also studied sex differences in the evolution and course of eating disorder symptoms from early adolescence to adulthood. Methods Using archival data from the QLSCD cohort, trajectories of eating disorder symptomatology were estimated from ages 12 to 20 years using semiparametric models. These trajectories included overall eating disorder symptomatology as measured by the SCOFF (Sick, Control, One Stone, Fat, Food), sex, and symptom-specific trajectories. Results Two groups of adolescents following distinct trajectories of eating disorder symptoms were identified. The first trajectory group included 30.9% of youth with sharply rising levels between 12 and 15 years, followed by high levels of symptoms between 15 and 20 years. The second trajectory group included 69.1% of youth with low and stable levels of symptoms between 12 and 20 years. Sex-specific models indicated that the proportion of girls in the high trajectory group was 1.3 times higher than the proportion of boys (42.8% girls vs. 32.3% boys). Trajectories of SCOFF items were similar for loss-of-control eating, feeling overweight, and attributing importance to food. The weight loss item had a different developmental pattern, increasing between 12 and 15 years and then decreasing between 17 and 20 years. Conclusions The largest increase in eating disorder symptoms in adolescence is between the ages of 12 and 15 . Yet, most prevention programs start after 15 years of age. Our findings suggest that, unlike common practices, eating disorder prevention programs should aim to start before puberty.