Social and non-social autism symptoms and trait domains are genetically dissociable

Jakob Grove,Hyejung Won,Ward De Witte,Anders D. Børglum,Simon Baron-Cohen,Varun Warrier,Roberto Toro,Richard Delorme,Thomas Bourgeron,David A. Hinds,Bhismadev Chakrabarti,Janita Bralten,Geert Poelmans,Freddy Cliquet,Claire S. Leblond

doi:10.1038/s42003-019-0558-4

Abstract

The core diagnostic criteria for autism comprise two symptom domains – social and communication difficulties, and unusually repetitive and restricted behaviour, interests and activities. There is some evidence to suggest that these two domains are dissociable, though this hypothesis has not yet been tested using molecular genetics. We test this using a genome-wide association study (N = 51,564) of a non-social trait related to autism, systemising, defined as the drive to analyse and build systems. We demonstrate that systemising is heritable and genetically correlated with autism. In contrast, we do not identify significant genetic correlations between social autistic traits and systemising. Supporting this, polygenic scores for systemising are significantly and positively associated with restricted and repetitive behaviour but not with social difficulties in autistic individuals. These findings strongly suggest that the two core domains of autism are genetically dissociable, and point at how to fractionate the genetics of autism.

Highlights

The core diagnostic criteria for autism comprise two symptom domains – social and communication difficulties, and unusually repetitive and restricted behaviour, interests and activities
To better understand the genetics of a non-social trait related to autism, we investigate the genetics of systemising measured using a 75-item well validated, self-report measure called the Systemising Quotient-Revised (SQR)
Several items in the SQ-R measure circumscribed interests and insistence on sameness, two of the items mentioned in the DSM-5, and several of these items map onto items on the Autism Spectrum Quotient (AQ), a well validated measure of autistic traits[27]

Summary

Introduction

The core diagnostic criteria for autism comprise two symptom domains – social and communication difficulties, and unusually repetitive and restricted behaviour, interests and activities. Most genetic research into the social and non-social domains has been primarily through linkage and genome-wide association studies (GWAS) in relatively small samples of autistic individuals and the general population (N < 5K)[19,20,21,22,23,24,25].

Results

Conclusion