Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 67,044 bioRxiv papers from 295,122 authors.
Ultra-rare disruptive and damaging mutations influence educational attainment in the general population
Daniel P Howrigan,
Seyedeh M. Zekavat,
Christopher W Whelan,
Michel G. Nivard,
Jonathan M Bloom,
Jacqueline I Goldstein,
Robert E Handsaker,
Elise B Robinson,
Shaun M. Purcell,
Mark J. Daly,
Steven A McCarroll,
Patrick F Sullivan,
Benjamin M Neale
Posted 07 Jun 2016
bioRxiv DOI: 10.1101/050195 (published DOI: 10.1038/nn.4404)
Posted 07 Jun 2016
Ultra-rare inherited and de novo disruptive variants in highly constrained (HC) genes are enriched in neurodevelopmental disorders. However, their impact on cognition in the general population has not been explored. We hypothesize that disruptive and damaging ultra-rare variants (URVs) in HC genes not only confer risk to neurodevelopmental disorders, but also influence general cognitive abilities measured indirectly by years of education (YOE). We tested this hypothesis in 14,133 individuals with whole exome or genome sequencing data. The presence of one or more URVs was associated with a decrease in YOE (3.1 months less for each additional mutation; P-value=3.3x10-8) and the effect was stronger in HC genes enriched for brain expression (6.5 months less, P-value=3.4x10-5). The effect of these variants was more pronounced than the estimated effects of runs of homozygosity and pathogenic copy number variation. Our findings suggest that effects of URVs in HC genes are not confined to severe neurodevelopmental disorder, but influence the cognitive spectrum in the general population.
- Downloaded 2,195 times
- Download rankings, all-time:
- Site-wide: 2,062 out of 67,044
- In genetics: 197 out of 3,773
- Year to date:
- Site-wide: 47,871 out of 67,044
- Since beginning of last month:
- Site-wide: 54,307 out of 67,044
Downloads over time
Distribution of downloads per paper, site-wide
- Top preprints of 2018
- Paper search
- Author leaderboards
- Overall metrics
- The API
- Email newsletter
- 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!