DNA Methylation of the Oxytocin Receptor Across Neurodevelopmental Disorders / Michelle T. SIU in Journal of Autism and Developmental Disorders, 51-10 (October 2021)  

Public ISBD [article]  inJournal of Autism and Developmental Disorders > 51-10 (October 2021) . - p.3610-3623 Titre : DNA Methylation of the Oxytocin Receptor Across Neurodevelopmental Disorders Type de document : texte imprimé Auteurs : Michelle T. SIU, Auteur ; Sabrina J. GOODMAN, Auteur ; Isaac YELLAN, Auteur ; Darci T. BUTCHER, Auteur ; Maryam JANGJOO, Auteur ; Daria GRAFODATSKAYA, Auteur ; Rageen RAJENDRAM, Auteur ; Youliang LOU, Auteur ; Rujun ZHANG, Auteur ; Chunhua ZHAO, Auteur ; Robert NICOLSON, Auteur ; Stelios GEORGIADES, Auteur ; Peter SZATMARI, Auteur ; Stephen SCHERER, Auteur ; Wendy ROBERTS, Auteur ; Evdokia ANAGNOSTOU, Auteur ; Rosanna WEKSBERG, Auteur Article en page(s) : p.3610-3623 Langues : Anglais (eng) Mots-clés : Attention Deficit Disorder with Hyperactivity/genetics  Autism Spectrum Disorder/genetics  DNA Methylation  Female  Humans  Male  Obsessive-Compulsive Disorder  Oxytocin/metabolism  Receptors, Oxytocin/genetics  Adhd  Asd  Ocd  Oxtr Index. décimale : PER Périodiques Résumé : Many neurodevelopmental disorders (NDDs) share common learning and behavioural impairments, as well as features such as dysregulation of the oxytocin hormone. Here, we examined DNA methylation (DNAm) in the 1st intron of the oxytocin receptor gene, OXTR, in patients with autism spectrum (ASD), attention deficit and hyperactivity (ADHD) and obsessive compulsive (OCD) disorders. DNAm of OXTR was assessed for cohorts of ASD (blood), ADHD (saliva), OCD (saliva), which uncovered sex-specific DNAm differences compared to neurotypical, tissue-matched controls. Individuals with ASD or ADHD exhibiting extreme DNAm values had lower IQ and more social problems, respectively, than those with DNAm within normative ranges. This suggests that OXTR DNAm patterns are altered across NDDs and may be correlated with common clinical outcomes. En ligne : http://dx.doi.org/10.1007/s10803-020-04792-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=453 [article] DNA Methylation of the Oxytocin Receptor Across Neurodevelopmental Disorders [texte imprimé] / Michelle T. SIU, Auteur ; Sabrina J. GOODMAN, Auteur ; Isaac YELLAN, Auteur ; Darci T. BUTCHER, Auteur ; Maryam JANGJOO, Auteur ; Daria GRAFODATSKAYA, Auteur ; Rageen RAJENDRAM, Auteur ; Youliang LOU, Auteur ; Rujun ZHANG, Auteur ; Chunhua ZHAO, Auteur ; Robert NICOLSON, Auteur ; Stelios GEORGIADES, Auteur ; Peter SZATMARI, Auteur ; Stephen SCHERER, Auteur ; Wendy ROBERTS, Auteur ; Evdokia ANAGNOSTOU, Auteur ; Rosanna WEKSBERG, Auteur . - p.3610-3623. Langues : Anglais (eng) in Journal of Autism and Developmental Disorders > 51-10 (October 2021) . - p.3610-3623 Mots-clés : Attention Deficit Disorder with Hyperactivity/genetics  Autism Spectrum Disorder/genetics  DNA Methylation  Female  Humans  Male  Obsessive-Compulsive Disorder  Oxytocin/metabolism  Receptors, Oxytocin/genetics  Adhd  Asd  Ocd  Oxtr Index. décimale : PER Périodiques Résumé : Many neurodevelopmental disorders (NDDs) share common learning and behavioural impairments, as well as features such as dysregulation of the oxytocin hormone. Here, we examined DNA methylation (DNAm) in the 1st intron of the oxytocin receptor gene, OXTR, in patients with autism spectrum (ASD), attention deficit and hyperactivity (ADHD) and obsessive compulsive (OCD) disorders. DNAm of OXTR was assessed for cohorts of ASD (blood), ADHD (saliva), OCD (saliva), which uncovered sex-specific DNAm differences compared to neurotypical, tissue-matched controls. Individuals with ASD or ADHD exhibiting extreme DNAm values had lower IQ and more social problems, respectively, than those with DNAm within normative ranges. This suggests that OXTR DNAm patterns are altered across NDDs and may be correlated with common clinical outcomes. En ligne : http://dx.doi.org/10.1007/s10803-020-04792-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=453

Obsessive-compulsive disorder and attention-deficit/hyperactivity disorder: distinct associations with DNA methylation and genetic variation / Sarah J. GOODMAN in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Obsessive-compulsive disorder and attention-deficit/hyperactivity disorder: distinct associations with DNA methylation and genetic variation Type de document : texte imprimé Auteurs : Sarah J. GOODMAN, Auteur ; Christie L. BURTON, Auteur ; Darci T. BUTCHER, Auteur ; Michelle T. SIU, Auteur ; Mathieu LEMIRE, Auteur ; Eric CHATER-DIEHL, Auteur ; Andrei L. TURINSKY, Auteur ; Michael BRUDNO, Auteur ; Noam SORENI, Auteur ; David ROSENBERG, Auteur ; Kate D. FITZGERALD, Auteur ; Gregory L. HANNA, Auteur ; Evdokia ANAGNOSTOU, Auteur ; Paul D. ARNOLD, Auteur ; Jennifer CROSBIE, Auteur ; Russell SCHACHAR, Auteur ; Rosanna WEKSBERG, Auteur Langues : Anglais (eng) Mots-clés : Attention Deficit Disorder with Hyperactivity/genetics  DNA Methylation/genetics  Genetic Variation/genetics  Humans  Obsessive-Compulsive Disorder/genetics  Adhd  Biomarker  DNA methylation  Epigenetics  Ocd Index. décimale : PER Périodiques Résumé : BACKGROUND: A growing body of research has demonstrated associations between specific neurodevelopmental disorders and variation in DNA methylation (DNAm), implicating this molecular mark as a possible contributor to the molecular etiology of these disorders and/or as a novel disease biomarker. Furthermore, genetic risk variants of neurodevelopmental disorders have been found to be enriched at loci associated with DNAm patterns, referred to as methylation quantitative trait loci (mQTLs). METHODS: We conducted two epigenome-wide association studies in individuals with attention-deficit/hyperactivity disorder (ADHD) or obsessive-compulsive disorder (OCD) (aged 4-18 years) using DNA extracted from saliva. DNAm data generated on the Illumina Human Methylation 450 K array were used to examine the interaction between genetic variation and DNAm patterns associated with these disorders. RESULTS: Using linear regression followed by principal component analysis, individuals with the most endorsed symptoms of ADHD or OCD were found to have significantly more distinct DNAm patterns from controls, as compared to all cases. This suggested that the phenotypic heterogeneity of these disorders is reflected in altered DNAm at specific sites. Further investigations of the DNAm sites associated with each disorder revealed that despite little overlap of these DNAm sites across the two disorders, both disorders were significantly enriched for mQTLs within our sample. CONCLUSIONS: Our DNAm data provide insights into the regulatory changes associated with genetic variation, highlighting their potential utility both in directing GWAS and in elucidating the pathophysiology of neurodevelopmental disorders. En ligne : https://dx.doi.org/10.1186/s11689-020-09324-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Obsessive-compulsive disorder and attention-deficit/hyperactivity disorder: distinct associations with DNA methylation and genetic variation [texte imprimé] / Sarah J. GOODMAN, Auteur ; Christie L. BURTON, Auteur ; Darci T. BUTCHER, Auteur ; Michelle T. SIU, Auteur ; Mathieu LEMIRE, Auteur ; Eric CHATER-DIEHL, Auteur ; Andrei L. TURINSKY, Auteur ; Michael BRUDNO, Auteur ; Noam SORENI, Auteur ; David ROSENBERG, Auteur ; Kate D. FITZGERALD, Auteur ; Gregory L. HANNA, Auteur ; Evdokia ANAGNOSTOU, Auteur ; Paul D. ARNOLD, Auteur ; Jennifer CROSBIE, Auteur ; Russell SCHACHAR, Auteur ; Rosanna WEKSBERG, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Attention Deficit Disorder with Hyperactivity/genetics  DNA Methylation/genetics  Genetic Variation/genetics  Humans  Obsessive-Compulsive Disorder/genetics  Adhd  Biomarker  DNA methylation  Epigenetics  Ocd Index. décimale : PER Périodiques Résumé : BACKGROUND: A growing body of research has demonstrated associations between specific neurodevelopmental disorders and variation in DNA methylation (DNAm), implicating this molecular mark as a possible contributor to the molecular etiology of these disorders and/or as a novel disease biomarker. Furthermore, genetic risk variants of neurodevelopmental disorders have been found to be enriched at loci associated with DNAm patterns, referred to as methylation quantitative trait loci (mQTLs). METHODS: We conducted two epigenome-wide association studies in individuals with attention-deficit/hyperactivity disorder (ADHD) or obsessive-compulsive disorder (OCD) (aged 4-18 years) using DNA extracted from saliva. DNAm data generated on the Illumina Human Methylation 450 K array were used to examine the interaction between genetic variation and DNAm patterns associated with these disorders. RESULTS: Using linear regression followed by principal component analysis, individuals with the most endorsed symptoms of ADHD or OCD were found to have significantly more distinct DNAm patterns from controls, as compared to all cases. This suggested that the phenotypic heterogeneity of these disorders is reflected in altered DNAm at specific sites. Further investigations of the DNAm sites associated with each disorder revealed that despite little overlap of these DNAm sites across the two disorders, both disorders were significantly enriched for mQTLs within our sample. CONCLUSIONS: Our DNAm data provide insights into the regulatory changes associated with genetic variation, highlighting their potential utility both in directing GWAS and in elucidating the pathophysiology of neurodevelopmental disorders. En ligne : https://dx.doi.org/10.1186/s11689-020-09324-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

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