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

Varun Warrier (1) , Roberto Toro (2) , Hyejung Won (3) , Claire S. Leblond (2) , Freddy Cliquet (2) , Richard Delorme (2, 4) , Ward de Witte (5) , Janita Bralten (5, 6) , Bhismadev Chakrabarti (1, 7) , Anders D. Børglum (8, 9) , Jakob Grove (8, 9) , Geert Poelmans (5) , 23andme Research Team , David A. Hinds (10) , Thomas Bourgeron (2) , Simon Baron-Cohen (1)

1 CAM - University of Cambridge [UK]
2 GHFC (UMR_3571 / U-Pasteur_1) - Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions
3 UNC - University of North Carolina [Chapel Hill]
4 Child and Adolescent Psychiatry Department [AP- HP Hôpital Robert Debré]
5 Radboud University Medical Center [Nijmegen]
6 Radboud University [Nijmegen]
7 UOR - University of Reading
8 iPSYCH - The Lundbeck Foundation Initiative for Integrative Psychiatric Research
9 Aarhus University [Aarhus]
10 23andMe Inc.

The core diagnostic criteria for autism comprise two symptom domainssocial 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.

Keywords: Autism spectrum disorders; Genetic predisposition to disease; Genome-wide association studies

Domains: Human genetics; Genomics [q-bio.GN]; Bioinformatics [q-bio.QM]

Varun Warrier, Roberto Toro, Hyejung Won, Claire S. Leblond, Freddy Cliquet, et al.. Social and non-social autism symptoms and trait domains are genetically dissociable. Communications Biology, 2019, 2 (1), pp.328. ⟨10.1038/s42003-019-0558-4⟩. ⟨pasteur-03261098⟩