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Genetic correlates of phenotypic heterogeneity in autism

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DOI

  • Varun Warrier, University of Cambridge
  • ,
  • Xinhe Zhang, University of Cambridge
  • ,
  • Patrick Reed, University of Cambridge
  • ,
  • Alexandra Havdahl, Norwegian Institute of Public Health, University of Oslo, Lovisenberg Diaconal Hospital
  • ,
  • Tyler M Moore, University of Pennsylvania
  • ,
  • Freddy Cliquet, Université de Paris Cité
  • ,
  • Claire S Leblond, Université de Paris Cité
  • ,
  • Thomas Rolland, Université de Paris Cité
  • ,
  • Anders Rosengren, iPSYCH -The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Københavns Universitet
  • ,
  • David H Rowitch, University of Cambridge
  • ,
  • Matthew E Hurles, Wellcome Sanger Institute
  • ,
  • Daniel H Geschwind, University of California
  • ,
  • Anders D Børglum
  • Elise B Robinson, Broad Institute of Harvard and MIT
  • ,
  • Jakob Grove
  • Hilary C Martin, Wellcome Sanger Institute
  • ,
  • Thomas Bourgeron, Université de Paris Cité
  • ,
  • Simon Baron-Cohen, University of Cambridge
  • ,
  • EU-AIMS LEAP
  • ,
  • iPSYCH-Autism Working Group
  • ,
  • Spectrum 10K and APEX Consortia

The substantial phenotypic heterogeneity in autism limits our understanding of its genetic etiology. To address this gap, here we investigated genetic differences between autistic individuals (nmax = 12,893) based on core and associated features of autism, co-occurring developmental disabilities and sex. We conducted a comprehensive factor analysis of core autism features in autistic individuals and identified six factors. Common genetic variants were associated with the core factors, but de novo variants were not. We found that higher autism polygenic scores (PGS) were associated with lower likelihood of co-occurring developmental disabilities in autistic individuals. Furthermore, in autistic individuals without co-occurring intellectual disability (ID), autism PGS are overinherited by autistic females compared to males. Finally, we observed higher SNP heritability for autistic males and for autistic individuals without ID. Deeper phenotypic characterization will be critical in determining how the complex underlying genetics shape cognition, behavior and co-occurring conditions in autism.

OriginalsprogEngelsk
TidsskriftNature Genetics
Vol/bind54
Nummer9
Sider (fra-til)1293-1304
Antal sider20
ISSN1061-4036
DOI
StatusUdgivet - sep. 2022

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