Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders
Daniel J. Weiner,
Emilie M. Wigdor,
Raymond K Walters,
Jack A. Kosmicki,
Kaitlin E Samocha,
David M Hougaard,
Preben Bo Mortensen,
George Davey Smith,
Mark J Daly,
Elise B Robinson,
iPSYCH-Broad Autism Group,
Psychiatric Genomics Consortium Autism Group
Posted 23 Nov 2016
bioRxiv DOI: 10.1101/089342 (published DOI: 10.1038/ng.3863)
Posted 23 Nov 2016
Autism spectrum disorder (ASD) risk is influenced by both common polygenic and de novo variation. The purpose of this analysis was to clarify the influence of common polygenic risk for ASDs and to identify subgroups of cases, including those with strong acting de novo variants, in which different types of polygenic risk are relevant. To do so, we extend the transmission disequilibrium approach to encompass polygenic risk scores, and introduce with polygenic transmission disequilibrium test. Using data from more than 6,400 children with ASDs and 15,000 of their family members, we show that polygenic risk for ASDs, schizophrenia, and educational attainment is over transmitted to children with ASDs in two independent samples, but not to their unaffected siblings. These findings hold independent of proband IQ. We find that common polygenic variation contributes additively to ASD risk in cases that carry a very strong acting de novo variant. Lastly, we find evidence that elements of polygenic risk are independent and differ in their relationship with proband phenotype. These results confirm that ASDs' genetic influences are highly additive and suggest that they create risk through at least partially distinct etiologic pathways.
- Downloaded 2,450 times
- Download rankings, all-time:
- Site-wide: 7,697
- In genetics: 316
- Year to date:
- Site-wide: 53,400
- Since beginning of last month:
- Site-wide: 121,265
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!