Limited contribution of rare, noncoding variation to autism spectrum disorder from sequencing of 2,076 genomes in quartet families
Donna M. Werling,
Matthew R Stone,
Joseph T Glessner,
Ryan L. Collins,
Ryan M. Layer,
Grace B Schwartz,
Benjamin B Currall,
Robert E Handsaker,
Jeffrey D Mandell,
Tomasz J. Nowakowski,
Michael F Walker,
Harold Z Wang,
Mathew J Waterman,
Arnold R. Kriegstein,
John L Rubenstein,
Steven A. McCarroll,
Ben M Neale,
A. Jeremy Willsey,
Mark J. Daly,
Matthew W. State,
Gabor T Marth,
Michael E. Talkowski,
Stephan J Sanders
Posted 13 Apr 2017
bioRxiv DOI: 10.1101/127043
Posted 13 Apr 2017
Genomic studies to date in autism spectrum disorder (ASD) have largely focused on newly arising mutations that disrupt protein coding sequence and strongly influence risk. We evaluate the contribution of noncoding regulatory variation across the size and frequency spectrum through whole genome sequencing of 519 ASD cases, their unaffected sibling controls, and parents. Cases carry a small excess of de novo (1.02-fold) noncoding variants, which is not significant after correcting for paternal age. Assessing 51,801 regulatory classes, no category is significantly associated with ASD after correction for multiple testing. The strongest signals are observed in coding regions, including structural variation not detected by previous technologies and missense variation. While rare noncoding variation likely contributes to risk in neurodevelopmental disorders, no category of variation has impact equivalent to loss-of-function mutations. Average effect sizes are likely to be smaller than that for coding variation, requiring substantially larger samples to quantify this risk.
- Downloaded 2,430 times
- Download rankings, all-time:
- Site-wide: 2,776 out of 93,394
- In genomics: 516 out of 5,875
- Year to date:
- Site-wide: 57,012 out of 93,394
- Since beginning of last month:
- Site-wide: 57,210 out of 93,394
Downloads over time
Distribution of downloads per paper, site-wide
- 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!