ASD and schizophrenia show distinct developmental profiles in common genetic overlap with population-based social communication difficulties

Beate St Pourcain*, Elise Robinson , Verneri Anttila, Brendan Bulik Sullivan, Julian Maller, Jean Golding, David Skuse, Susan Ring, David Evans, Stanley Zammit, Simon Fisher, Benjamin Neale, Richard Anney, Stephen Ripke, Mads Hollegaard, Thomas Werge, Angelica Ronald, Jakob Grove, David Hougaard, Anders BorglumPreben Bo Mortensen, Mark Daly, George Davey Smith

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

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Abstract

Difficulties in social communication are part of the phenotypic overlap between autism spectrum disorders (ASD) and schizophrenia. Both conditions follow, however, distinct developmental patterns. Symptoms of ASD typically occur during early childhood, whereas most symptoms characteristic of schizophrenia do not appear before early adulthood. We investigated whether overlap in common genetic influences between these clinical conditions and impairments in social communication depends on the developmental stage of the assessed trait. Social communication difficulties were measured in typically-developing youth (Avon Longitudinal Study of Parents and Children, N≤5553, longitudinal assessments at 8, 11, 14 and 17 years) using the Social Communication Disorder Checklist. Data on clinical ASD (PGC-ASD: 5305 cases, 5305 pseudo-controls; iPSYCH-ASD: 7783 cases, 11 359 controls) and schizophrenia (PGC-SCZ2: 34 241 cases, 45 604 controls, 1235 trios) were either obtained through the Psychiatric Genomics Consortium (PGC) or the Danish iPSYCH project. Overlap in genetic influences between ASD and social communication difficulties during development decreased with age, both in the PGC-ASD and the iPSYCH-ASD sample. Genetic overlap between schizophrenia and social communication difficulties, by contrast, persisted across age, as observed within two independent PGC-SCZ2 subsamples, and showed an increase in magnitude for traits assessed during later adolescence. ASD-and schizophrenia-related polygenic effects were unrelated to each other and changes in trait-disorder links reflect the heterogeneity of genetic factors influencing social communication difficulties during childhood versus later adolescence. Thus, both clinical ASD and schizophrenia share some genetic influences with impairments in social communication, but reveal distinct developmental profiles in their genetic links, consistent with the onset of clinical symptoms.

Original languageEnglish
Pages (from-to)263-270
Number of pages8
JournalMolecular Psychiatry
Volume23
Issue number2
Early online date3 Jan 2017
DOIs
Publication statusPublished - Feb 2018

Keywords

  • Autism spectrum disorder
  • ALSPAC
  • schizophrenia
  • social communication
  • GWAS

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