Identification of common genetic risk variants for autism spectrum disorder

Jakob Grove, Abdel Abdellaoui, Eske M. Derks, Conor V. Dolan, Jouke Jan Hottenga, Rick Jansen, Hamdi Mbarek, Christel M. Middeldorp, Yuri Milaneschi, Michel G. Nivard, Danielle Posthuma, Gonneke Willemsen, Dorret I. Boomsma, E. J.C. de Geus, Brenda W.J.H. Penninx, Anders D. Børglum*, Autism Spectrum Disorder Working Group of the Psychiatric Genomics Consortium, BUPGEN, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, 23Andme Research Team

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

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Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD.

Original languageEnglish
Pages (from-to)431-444
Number of pages14
JournalNature Genetics
Issue number3
Publication statusPublished - Mar 2019


FundersFunder number
National Institute of Diabetes and Digestive and Kidney DiseasesK01DK114379

    Cohort Studies

    • Netherlands Twin Register (NTR)


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