Polygenic scores for intelligence, educational attainment and schizophrenia are differentially associated with core autism features, IQ, and adaptive behaviour in autistic individuals
Résumé
Importance
Schizophrenia, educational attainment, and intelligence are all genetically correlated with autism. However, autism is a complex condition, with several different core (such as social communication difficulties and repetitive and restricted behaviour) and associated features (such as IQ and adaptive behaviour) contributing to the underlying heterogeneity. It is unknown to what extent polygenic scores (PGS) for these three phenotypes are associated with the core and associated autism features.
Objective
To investigate the association of PGS for intelligence, educational attainment and schizophrenia on core autism features, IQ and adaptive behaviour in autistic individuals. To further investigate the effects of stratifying by sex and IQ on these associations.
Design
PGS association for the three phenotypes with 12 different autism core and associated features in three cohorts followed by meta-analysis. We additionally conducted sensitivity analyses by stratifying for sex and IQ.
Settings :
Three cross-sectional, multi-centre cohorts comprising autistic with genotype data, and phenotypic information.
Participants
Autistic individuals (total N: 2,512 – 3,681) from three different cohorts: Simons Simplex Collection (Nmax = 2,233), Autism Genetic Research Exchange (Nmax = 1,200), and AIMS-2- TRIALS LEAP (Nmax = 262)
Main outcome measures
Association of PGS for intelligence, educational attainment, and schizophrenia with core autism features, measures of intelligence, and adaptive behaviour in autistic individuals
Results
We identified a similar pattern of correlation among core and associated autism features across all three cohorts. Cluster analyses of these features identified two broad clusters – one consisting of the core features, and another consisting of IQ and adaptive behaviour. PGS for intelligence were only associated with measures of intelligence and adaptive behaviour (e.g. for full-scale IQ, Beta = 0.08, 95%CI = 0.11 – 0.04) for PGS for educational attainment were associated for measures of intelligence, adaptive behaviour, and additionally, non-verbal communication as measured by ADI – a core-autism feature (e.g. for full-scale IQ, Beta = 0.05, 95%CI = 0.08 – 0.02; for ADI non-verbal communication, Beta = 0.05, 95%CI = 0.09 – 0.01). Finally, PGS for schizophrenia were associated with two core autism features: restricted and repetitive behaviour and verbal communication difficulties as measured by the ADI-R (e.g. for ADI restricted and repetitive behaviour: Beta = 0.06, 95%CI = 0.09 – 0.02). Most of these associations were also significant when restricting it to males only or to individuals with IQ > 70. We find limited evidence for heterogeneity between cohorts.
Conclusion and relevance
We identify specific and different patterns of association between PGS for the three phenotypes and core and associated autism features. This provides greater resolution into the shared genetics between autism and the three phenotypes, and suggests one method to investigate heterogeneity in autism and co-occurring conditions.
Origine : Fichiers produits par l'(les) auteur(s)
