Common Genetic Variation in Neuropeptide Receptors and Social Processing Across Neurodevelopmental Disorders

Thursday, May 12, 2016: 11:30 AM-1:30 PM
Hall A (Baltimore Convention Center)
D. A. Baribeau1, A. Dupuis2, T. A. Paton3, S. W. Scherer4, R. Schachar5, P. D. Arnold6, P. Szatmari7, R. Nicolson8, S. Georgiades9, N. Soreni9, J. Crosbie2, J. A. Brian10, A. Iaboni11 and E. Anagnostou1, (1)University of Toronto, Toronto, ON, Canada, (2)The Hospital for Sick Children, Toronto, ON, Canada, (3)the Centre for Applied Genomics at the Hospital for Sick Children, Toronto, ON, Canada, (4)Centre for Applied Genomics (TCAG), Hospital for Sick Children, Toronto, ON, Canada, (5)Psychiatry, The Hospital for Sick Children, Toronto, ON, Canada, (6)University of Calgary, Calgary, AB, Canada, (7)Centre for Addiction and Mental Health, Toronto, ON, Canada, (8)University of Western Ontario, London, ON, Canada, (9)McMaster University, Hamilton, ON, Canada, (10)Bloorview Research Institute, Toronto, ON, Canada, (11)Holland Bloorview Kids Rehabilitation Hospital, Toronto, ON, Canada
Background:   Common genetic variation in the oxytocin receptor (OXTR) and vasopressin receptor (AVPR1a) genes has been associated with differences in social abilities in typically developing individuals and in those with autism spectrum disorder (ASD). Whether common genetic variation in OXTR or AVPR1a also affects social abilities to the same degree in other neurodevelopmental disorders is unknown.

Objectives: To examine the effects of common genetic variation in the oxytocin receptor (OXTR) and vasopressin receptor (AVPR1a) genes, on social communication and perception abilities across different childhood onset neurodevelopmental disorders.

Methods:   Children with autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), or obsessive-compulsive disorder (OCD) (n=253), completed a standardized social perception task (Reading the Mind in the Eyes Test-RMET) and their parents/caregivers completed the Social Communication Questionnaire (SCQ). DNA from blood/saliva was analyzed to determine individual genotypes for 5 OXTR single nucleotide polymorphisms (SNPs) and AVPR1a RS3 microsatellite length. Social communication, as measured by the SCQ, and social perception abilities, as measured by the RMET, were compared by genotype using regression models, while controlling for differences in age, sex, ancestry and IQ. Significant findings were examined for interactions with diagnosis.

Results: Social communication abilities varied significantly by genotype for one OXTR SNP (OXTR rs53576) and showed a trend towards an association for another (OXTR rs237887) (p = 0.007, and p = 0.05 respectively). For OXTR rs237887, secondary pairwise comparisons of RMET scores by genotype revealed a pattern congruent with SCQ scores.  Length of AVPR1a RS3 did not impact social communication or perception abilities. For analyses involving OXTR rs53576, genotype effects on SCQ scores were highly significant in the group with ASD only (p ≤ 0.0001), with no significant effects detected in the other diagnostic groups.  Specific allele pairs in combination [OXTR rs53576 (GG) and OXTR rs237887 (AA)] were associated with greater social communication deficits.

Conclusions:   Common genetic variation in OXTR, but not AVPR1a, was associated with variable social communication abilities across neurodevelopmental disorders in this sample, suggesting that common variation may play a role in modifying severity of social impairment. Children with ASD may be more sensitive to this effect.