Integrating healthcare and research genetic data empowers the discovery of 49 novel developmental disorders
Kaitlin E. Samocha,
Kevin J. Arvai,
Ruth Y. Eberhardt,
Stefan H. Lelieveld,
Hilary C. Martin,
Jeremy F McRae,
Patrick J. Short,
Rebecca I. Torene,
Elke de Boer,
Eugene J. Gardner,
Margot R. F. Reijnders,
Helger G. Yntema,
Lisenka E. L. M. Vissers,
Caroline F. Wright,
Han G Brunner,
Helen V. Firth,
David R. FitzPatrick,
Jeffrey C Barrett,
Matthew E Hurles,
Posted 02 Feb 2018
bioRxiv DOI: 10.1101/258723
Posted 02 Feb 2018
De novo mutations (DNMs) in protein-coding genes are a well-established cause of developmental disorders (DD). However, known DD-associated genes only account for a minority of the observed excess of such DNMs. To identify novel DD-associated genes, we integrated healthcare and research exome sequences on 31,058 DD parent-offspring trios, and developed a simulation-based statistical test to identify gene-specific enrichments of DNMs. We identified 299 significantly DD-associated genes, including 49 not previously robustly associated with DDs. Despite detecting more DD-associated genes than in any previous study, much of the excess of DNMs of protein-coding genes remains unaccounted for. Modelling suggests that over 500 novel DD-associated genes await discovery, many of which are likely to be less penetrant than the currently known genes. Research access to clinical diagnostic datasets will be critical for completing the map of dominant DDs.
- Downloaded 1,043 times
- Download rankings, all-time:
- Site-wide: 11,160 out of 92,253
- In genomics: 1,569 out of 5,819
- Year to date:
- Site-wide: 28,037 out of 92,253
- Since beginning of last month:
- Site-wide: 42,800 out of 92,253
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!