Genetic correlates of phenotypic heterogeneity in autism
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Published:2022-06-02
Issue:9
Volume:54
Page:1293-1304
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ISSN:1061-4036
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Container-title:Nature Genetics
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language:en
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Short-container-title:Nat Genet
Author:
Warrier VarunORCID, Zhang Xinhe, Reed Patrick, Havdahl AlexandraORCID, Moore Tyler M.ORCID, Cliquet Freddy, Leblond Claire S., Rolland Thomas, Rosengren AndersORCID, Caceres Antonia San Jose, Hayward Hannah, Crawley Daisy, Faulkner Jessica, Sabet Jessica, Ellis Claire, Oakley Bethany, Loth Eva, Charman Tony, Murphy Declan, Holt Rosemary, Waldman Jack, Upadhyay Jessica, Gunby Nicola, Lai Meng-Chuan, Renouf Gwilym, Ruigrok Amber, Taylor Emily, Ziauddeen Hisham, Deakin Julia, di Bruttopilo Sara Ambrosino, van Dijk Sarai, Rijks Yvonne, Koops Tabitha, Douma Miriam, Spaan Alyssia, Selten Iris, Steffers Maarten, van Themaat Anna Ver Loren, Bast Nico, Baumeister Sarah, O’Dwyer Larry, Bours Carsten, Rausch Annika, von Rhein Daniel, Cornelissen Ineke, de Bruin Yvette, Graauwmans Maartje, Kostrzewa Elzbieta, Cauvet Elodie, Tammimies Kristiina, Sitnikow Rouslan, Dumas Guillaume, Kim Yang-Min, Bourgeron ThomasORCID, Hougaard David M., Bybjerg-Grauholm Jonas, Werge Thomas, Mortensen Preben Bo, Mors Ole, Nordentoft Merete, Adhya Dwaipayan, Alamanza Armandina, Allison Carrie, Garvey Isabelle, Parsons Tracey, Smith Paula, Tsompanidis Alex, Burton Graham J., Heazell Alexander E. P., Gabis Lidia V., Biron-Shental Tal, Lancaster Madeline A., Srivastava Deepak P., Mill Jonathan, Rowitch David H., Hurles Matthew E.ORCID, Geschwind Daniel H.ORCID, Børglum Anders D.ORCID, Robinson Elise B., Grove JakobORCID, Martin Hilary C.ORCID, Bourgeron ThomasORCID, Baron-Cohen SimonORCID, , ,
Abstract
AbstractThe 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.
Funder
Wellcome Trust Templeton World Charity Foundation
Publisher
Springer Science and Business Media LLC
Reference100 articles.
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