Identification of common genetic risk variants for autism spectrum disorder

By J. Grove, S. Ripke, T. Als, M. Mattheisen, R. Walters, H. Won, Jonatan Pallesen, E. Agerbo, O. Andreassen, R. Anney and 266 more. Nature Genetics, 2019

2,059 citations recorded by the source corpus.

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. A genome-wide-association meta-analysis of 18,381 austim spectrum disorder (ASD) cases and 27,969 controls identifies five risk loci. The authors find quantitative and qualitative polygenic heterogeneity across ASD subtypes.

Subfields: Cognitive Neuroscience, Genetics

View Paper: https://www.semanticscholar.org/paper/de76bc22bc90bdf00218710f1725447440454816

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Citations in the corpus

Genomic relationships, novel loci, and pleiotropic mechanisms across eight psychiatric disorders (2019, background): “As expected, the associated traits included SCZ, BIP, and ASD.”
The genetic architecture of the human cerebral cortex (2020, methodology): “Summary statistics were downloaded from the following published genome-wide association studies: general cognitive function(45), insomnia(47), antisocial behavior(62), educational attainment(21), subjective well-being(49), depressive symptoms(49), neuroticism(51), attention deficit hyperactivity dis”
Transcriptome-scale spatial gene expression in the human dorsolateral prefrontal cortex (2020, background): “…specific laminar associations with penetrant de novo variants were in contrast to broad laminar enrichments of genes differentially expressed in the brains of patients with ASD (Gandal et al., 2018) and lack of laminar enrichment of genes implicated by common genetic variation (Grove et al., 2019).”
Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism (2019, methodology): “Notably, among the ﬁve GWAS-signiﬁcant ASD hits (Grove etal.,2019), KMT2E isimplicatedbybothGWASandthelistof102 FDR % 0.1 genes described here (Fisher’s exact test, p = 0.029).”