Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 62,232 bioRxiv papers from 276,305 authors.
Linkage disequilibrium dependent architecture of human complex traits reveals action of negative selection
Hilary K Finucane,
Nicholas A. Furlotte,
Pier Francesco Palamara,
Benjamin M Neale,
Alkes L. Price
Posted 19 Oct 2016
bioRxiv DOI: 10.1101/082024 (published DOI: 10.1038/ng.3954)
Posted 19 Oct 2016
Recent work has hinted at the linkage disequilibrium (LD) dependent architecture of human complex traits, where SNPs with low levels of LD (LLD) have larger per-SNP heritability after conditioning on their minor allele frequency (MAF). However, this has not been formally assessed, quantified or biologically interpreted. Here, we analyzed summary statistics from 56 complex diseases and traits (average N = 101,401) by extending stratified LD score regression to continuous annotations. We determined that SNPs with low LLD have significantly larger per-SNP heritability. Roughly half of the LLD signal can be explained by functional annotations that are negatively correlated with LLD, such as DNase I hypersensitivity sites (DHS). The remaining signal is largely driven by our finding that common variants that are more recent tend to have lower LLD and to explain more heritability (P = 2.38 x 10-104); the youngest 20% of common SNPs explain 3.9x more heritability than the oldest 20%, consistent with the action of negative selection. We also inferred jointly significant effects of other LD-related annotations and confirmed via forward simulations that these annotations jointly predict deleterious effects. Our results are consistent with the action of negative selection on deleterious variants that affect complex traits, complementing efforts to learn about negative selection by analyzing much smaller rare variant data sets.
- Downloaded 2,531 times
- Download rankings, all-time:
- Site-wide: 1,433 out of 62,232
- In genetics: 138 out of 3,538
- Year to date:
- Site-wide: 21,996 out of 62,232
- Since beginning of last month:
- Site-wide: 22,359 out of 62,232
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!