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Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders

Autism spectrum disorder (ASD) risk is influenced by common polygenic and de novo variation. We aimed to clarify the influence of polygenic risk for ASDs and to identify subgroups of ASD cases, including those with strong acting de novo variants, in which polygenic risk is relevant. Using a novel ap...

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Detalles Bibliográficos
Autores principales: Weiner, Daniel J., Wigdor, Emilie M., Ripke, Stephan, Walters, Raymond K., Kosmicki, Jack A., Grove, Jakob, Samocha, Kaitlin E., Goldstein, Jacqueline, Okbay, Aysu, Bybjerg-Grauholm, Jonas, Werge, Thomas, Hougaard, David M., Taylor, Jacob, Skuse, David, Devlin, Bernie, Anney, Richard, Sanders, Stephan J., Bishop, Somer, Mortensen, Preben Bo, Børglum, Anders D., Smith, George Davey, Daly, Mark J., Robinson, Elise B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5552240/
https://www.ncbi.nlm.nih.gov/pubmed/28504703
http://dx.doi.org/10.1038/ng.3863
Descripción
Sumario:Autism spectrum disorder (ASD) risk is influenced by common polygenic and de novo variation. We aimed to clarify the influence of polygenic risk for ASDs and to identify subgroups of ASD cases, including those with strong acting de novo variants, in which polygenic risk is relevant. Using a novel approach called the polygenic transmission disequilibrium test, and data from 6,454 families with a child with ASD, we show that polygenic risk for ASDs, schizophrenia, and greater educational attainment is over transmitted to children with ASDs. These findings hold independent of proband IQ. We find that polygenic variation contributes additively to risk in ASD cases who carry a strong acting de novo variant. Lastly, we show that elements of polygenic risk are independent and differ in their relationship with phenotype. These results confirm that ASDs’ genetic influences are additive and suggest they create risk through at least partially distinct etiologic pathways.