DNA methylation at the DMPK gene locus is associated with cognitive functions in myotonic dystrophy type 1.
Édith BretonCécilia LégaréGayle OverendSimon-Pierre GuayDarren G MoncktonJean MathieuCynthia GagnonLouis RicherBenjamin GallaisLuigi BouchardPublished in: Epigenomics (2020)
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.
Keyphrases
- dna methylation
- end stage renal disease
- genome wide
- newly diagnosed
- chronic kidney disease
- ejection fraction
- gene expression
- prognostic factors
- early onset
- adipose tissue
- type diabetes
- machine learning
- mild cognitive impairment
- patient reported outcomes
- electronic health record
- high resolution
- single molecule
- deep learning
- atomic force microscopy
- weight loss
- genome wide identification
- high speed