Xue, Y;
Mezzavilla, M;
Haber, M;
McCarthy, S;
Chen, Y;
Narasimhan, V;
Gilly, A;
... Zeggini, E; + view all
(2017)
Enrichment of low-frequency functional variants revealed by whole-genome sequencing of multiple isolated European populations.
Nature Communications
, 8
, Article 15927. 10.1038/ncomms15927.
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Abstract
The genetic features of isolated populations can boost power in complex-trait association studies, and an in-depth understanding of how their genetic variation has been shaped by their demographic history can help leverage these advantageous characteristics. Here, we perform a comprehensive investigation using 3,059 newly generated low-depth whole-genome sequences from eight European isolates and two matched general populations, together with published data from the 1000 Genomes Project and UK10K. Sequencing data give deeper and richer insights into population demography and genetic characteristics than genotype-chip data, distinguishing related populations more effectively and allowing their functional variants to be studied more fully. We demonstrate relaxation of purifying selection in the isolates, leading to enrichment of rare and low-frequency functional variants, using novel statistics, DVxy and SVxy. We also develop an isolation-index (Isx) that predicts the overall level of such key genetic characteristics and can thus help guide population choice in future complex-trait association studies.
| Type: | Article |
|---|---|
| Title: | Enrichment of low-frequency functional variants revealed by whole-genome sequencing of multiple isolated European populations |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/ncomms15927 |
| Publisher version: | https://doi.org/10.1038/ncomms15927 |
| Language: | English |
| Additional information: | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, LINKAGE DISEQUILIBRIUM, GENETIC-CHARACTERIZATION, RARE VARIANT, SIZE, ASSOCIATION, INDIVIDUALS, ADAPTATION, SELECTION, IDENTITY, DESCENT |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10082286 |
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