DNA Methylation of the Oxytocin Receptor Across Neurodevelopmental Disorders

Michelle T Siu; Sarah J Goodman; Isaac Yellan; Darci T Butcher; Maryam Jangjoo; Daria Grafodatskaya; Rageen Rajendram; Youliang Lou; Rujun Zhang; Chunhua Zhao; Rob Nicolson; Stelios Georgiades; Peter Szatmari; Stephen W Scherer; Wendy Roberts; Evdokia Anagnostou; Rosanna Weksberg

doi:10.1007/s10803-020-04792-x

DNA Methylation of the Oxytocin Receptor Across Neurodevelopmental Disorders

J Autism Dev Disord. 2021 Oct;51(10):3610-3623. doi: 10.1007/s10803-020-04792-x. Epub 2021 Jan 4.

Authors

Michelle T Siu^{1

2

3}, Sarah J Goodman³, Isaac Yellan^{3

4}, Darci T Butcher^{3

5}, Maryam Jangjoo³, Daria Grafodatskaya⁵, Rageen Rajendram³, Youliang Lou³, Rujun Zhang³, Chunhua Zhao³, Rob Nicolson⁶, Stelios Georgiades⁷, Peter Szatmari^{8

9}, Stephen W Scherer^{3

4

10

11}, Wendy Roberts³, Evdokia Anagnostou^{12

13}, Rosanna Weksberg^{14

15

16

17}

Affiliations

¹ Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
² Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
³ Genetics and Genome Biology, Hospital for Sick Children, Toronto, ON, Canada.
⁴ Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
⁵ Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
⁶ Department of Psychiatry, University of Western Ontario, London, ON, Canada.
⁷ Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada.
⁸ The Margaret and Wallace McCain Centre for Child, Youth & Family Mental Health and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
⁹ Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
¹⁰ The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON, Canada.
¹¹ McLaughlin Centre, University of Toronto, Toronto, ON, Canada.
¹² Holland Bloorview Kids Rehabilitation Hospital, Toronto, ON, Canada.
¹³ Department of Pediatrics, University of Toronto, Toronto, ON, Canada.
¹⁴ Genetics and Genome Biology, Hospital for Sick Children, Toronto, ON, Canada. rweksb@sickkids.ca.
¹⁵ Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada. rweksb@sickkids.ca.
¹⁶ Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, 555 University Ave, Toronto, ON, M5G 1X8, Canada. rweksb@sickkids.ca.
¹⁷ Institute of Medical Science, School of Graduate Studies, University of Toronto, Toronto, ON, Canada. rweksb@sickkids.ca.

PMID: 33394241
DOI: 10.1007/s10803-020-04792-x

Abstract

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.

Keywords: ADHD; ASD; DNA methylation; OCD; OXTR.

MeSH terms

Attention Deficit Disorder with Hyperactivity* / genetics
Autism Spectrum Disorder* / genetics
DNA Methylation
Female
Humans
Male
Obsessive-Compulsive Disorder*
Oxytocin / metabolism
Receptors, Oxytocin / genetics

Substances

Receptors, Oxytocin
Oxytocin