Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 66,819 bioRxiv papers from 294,207 authors.
Ultra-rare variants drive substantial cis-heritability of human gene expression
By
Ryan D. Hernandez,
Lawrence H. Uricchio,
Kevin Hartman,
Chun Ye,
Andrew Dahl,
Noah Zaitlen
Posted 14 Nov 2017
bioRxiv DOI: 10.1101/219238
(published DOI: 10.1038/s41588-019-0487-7)
The vast majority of human mutations have minor allele frequencies (MAF) under 1%, with the plurality observed only once (i.e., “singletons”). While Mendelian diseases are predominantly caused by rare alleles, their cumulative contribution to complex phenotypes remains largely unknown. We develop and rigorously validate an approach to jointly estimate the contribution of all alleles, including singletons, to phenotypic variation. We apply our approach to transcriptional regulation, an intermediate between genetic variation and complex disease. Using whole genome DNA and lymphoblastoid cell line RNA sequencing data from 360 European individuals, we conservatively estimate that singletons contribute ~25% of cis-heritability across genes (dwarfing the contributions of other frequencies). Strikingly, the majority (~76%) of singleton heritability derives from ultra-rare variants absent from thousands of additional samples. We develop a novel inference procedure to demonstrate that our results are consistent with rampant purifying selection shaping the regulatory architecture of most human genes.
Download data
- Downloaded 2,616 times
- Download rankings, all-time:
- Site-wide: 1,483 out of 66,819
- In evolutionary biology: 62 out of 4,441
- Year to date:
- Site-wide: 2,074 out of 66,819
- Since beginning of last month:
- Site-wide: 5,481 out of 66,819
Altmetric data
Downloads over time
Distribution of downloads per paper, site-wide
- Home
- Top preprints of 2018
- Paper search
- Author leaderboards
- Overall metrics
- The API
- Email newsletter
- About
News
- 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!