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 ASD and to identify subgroups of ASD cases, including those with strongly acting de novo variants, in which polygenic risk is relevant. Using a novel a...

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Main Authors: Walters, RK, Kosmicki, JA, Grove, J, Samocha, KE, Goldstein, JI, Okbay, A, Bybjerg-Grauholm, J, Werge, T, Hougaard, DM, Taylor, J, iPSYCH-Broad Autism Group, Psychiatric Genomics Consortium Autism Group, Skuse, D, Devlin, B, Anney, R, Sanders, SJ, Bishop, S, Mortensen, PB, Børglum, AD, Smith, GD, Daly, MJ, Robinson, EB
Other Authors: Wallace, S
Format: Journal article
Language:English
Published: Nature Research 2017
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author Walters, RK
Kosmicki, JA
Grove, J
Samocha, KE
Goldstein, JI
Okbay, A
Bybjerg-Grauholm, J
Werge, T
Hougaard, DM
Taylor, J
iPSYCH-Broad Autism Group
Psychiatric Genomics Consortium Autism Group
Skuse, D
Devlin, B
Anney, R
Sanders, SJ
Bishop, S
Mortensen, PB
Børglum, AD
Smith, GD
Daly, MJ
Robinson, EB
author2 Wallace, S
author_facet Wallace, S
Walters, RK
Kosmicki, JA
Grove, J
Samocha, KE
Goldstein, JI
Okbay, A
Bybjerg-Grauholm, J
Werge, T
Hougaard, DM
Taylor, J
iPSYCH-Broad Autism Group
Psychiatric Genomics Consortium Autism Group
Skuse, D
Devlin, B
Anney, R
Sanders, SJ
Bishop, S
Mortensen, PB
Børglum, AD
Smith, GD
Daly, MJ
Robinson, EB
author_sort Walters, RK
collection OXFORD
description Autism spectrum disorder (ASD) risk is influenced by common polygenic and de novo variation. We aimed to clarify the influence of polygenic risk for ASD and to identify subgroups of ASD cases, including those with strongly 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 ASD, schizophrenia, and greater educational attainment is over-transmitted to children with ASD. These findings hold independent of proband IQ. We find that polygenic variation contributes additively to risk in ASD cases who carry a strongly 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 the genetic influences on ASD are additive and suggest that they create risk through at least partially distinct etiologic pathways.
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spelling oxford-uuid:631ad89b-64df-4979-9d77-ac2baf20a5992022-03-26T18:10:41ZPolygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:631ad89b-64df-4979-9d77-ac2baf20a599EnglishSymplectic ElementsNature Research2017Walters, RKKosmicki, JAGrove, JSamocha, KEGoldstein, JIOkbay, ABybjerg-Grauholm, JWerge, THougaard, DMTaylor, JiPSYCH-Broad Autism GroupPsychiatric Genomics Consortium Autism GroupSkuse, DDevlin, BAnney, RSanders, SJBishop, SMortensen, PBBørglum, ADSmith, GDDaly, MJRobinson, EBWallace, SBailey, AJMonaco, APPagnamenta, AAutism spectrum disorder (ASD) risk is influenced by common polygenic and de novo variation. We aimed to clarify the influence of polygenic risk for ASD and to identify subgroups of ASD cases, including those with strongly 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 ASD, schizophrenia, and greater educational attainment is over-transmitted to children with ASD. These findings hold independent of proband IQ. We find that polygenic variation contributes additively to risk in ASD cases who carry a strongly 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 the genetic influences on ASD are additive and suggest that they create risk through at least partially distinct etiologic pathways.
spellingShingle Walters, RK
Kosmicki, JA
Grove, J
Samocha, KE
Goldstein, JI
Okbay, A
Bybjerg-Grauholm, J
Werge, T
Hougaard, DM
Taylor, J
iPSYCH-Broad Autism Group
Psychiatric Genomics Consortium Autism Group
Skuse, D
Devlin, B
Anney, R
Sanders, SJ
Bishop, S
Mortensen, PB
Børglum, AD
Smith, GD
Daly, MJ
Robinson, EB
Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders.
title Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders.
title_full Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders.
title_fullStr Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders.
title_full_unstemmed Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders.
title_short Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders.
title_sort polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders
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