Journal article
Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders
Nature genetics, Vol.49(7), pp.978-985
07/2017
DOI: 10.1038/ng.3863
PMCID: PMC5552240
PMID: 28504703
Abstract
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.
Details
- Title: Subtitle
- Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders
- Creators
- Jack A Kosmicki - Massachusetts General HospitalJakob Grove - Aarhus UniversityKaitlin E Samocha - Broad InstituteJacqueline I Goldstein - Broad InstituteAysu Okbay - Vrije Universiteit AmsterdamJonas Bybjerg-Grauholm - Statens Serum InstitutThomas Werge - University of CopenhagenDavid M Hougaard - Statens Serum InstitutJacob Taylor - Massachusetts General HospitalDavid Skuse - University College LondonBernie Devlin - University of PittsburghRichard Anney - Cardiff UniversityStephan J Sanders - University of California, San FranciscoSomer Bishop - University of California, San FranciscoPreben Bo Mortensen - Aarhus UniversityAnders D Børglum - Aarhus UniversityGeorge Davey Smith - University of BristolDaniel J Weiner - Broad InstituteEmilie M Wigdor - Broad InstituteMark J Daly - Broad InstituteStephan Ripke - Massachusetts General HospitalElise B Robinson - Broad InstituteRaymond K Walters - Broad InstituteiPSYCH-Broad Autism Group
- Contributors
- Thomas H Wassink (Contributor) - University of Iowa, Psychiatry
- Resource Type
- Journal article
- Publication Details
- Nature genetics, Vol.49(7), pp.978-985
- DOI
- 10.1038/ng.3863
- PMID
- 28504703
- PMCID
- PMC5552240
- NLM abbreviation
- Nat Genet
- ISSN
- 1061-4036
- eISSN
- 1546-1718
- Grant note
- R01 MH094293 / NIMH NIH HHS MR/L010305/1 / Medical Research Council U54 HD086984 / NICHD NIH HHS R01 MH100027 / NIMH NIH HHS U01 MH094432 / NIMH NIH HHS R00 MH101367 / NIMH NIH HHS P30 ES013508 / NIEHS NIH HHS MC_UU_12013/1 / Medical Research Council 647648 / European Research Council K01 MH099286 / NIMH NIH HHS U01 MH109539 / NIMH NIH HHS U01 MH109514 / NIMH NIH HHS
- Language
- English
- Date published
- 07/2017
- Academic Unit
- Psychiatry; Stead Family Department of Pediatrics
- Record Identifier
- 9984281756302771
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