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The UK10K project identifies rare variants in health and disease.

UK10K Consortium, ; Walter, K; Min, JL; Huang, J; Crooks, L; Memari, Y; McCarthy, S; Perry, JRB; Xu, C; Futema, M; et al. UK10K Consortium; Walter, K; Min, JL; Huang, J; Crooks, L; Memari, Y; McCarthy, S; Perry, JRB; Xu, C; Futema, M; Lawson, D; Iotchkova, V; Schiffels, S; Hendricks, AE; Danecek, P; Li, R; Floyd, J; Wain, LV; Barroso, I; Humphries, SE; Hurles, ME; Zeggini, E; Barrett, JC; Plagnol, V; Richards, JB; Greenwood, CMT; Timpson, NJ; Durbin, R; Soranzo, N (2015) The UK10K project identifies rare variants in health and disease. Nature, 526 (7571). pp. 82-90. ISSN 1476-4687 https://doi.org/10.1038/nature14962
SGUL Authors: Whincup, Peter Hynes Curran, Sarah Rosario Jamshidi, Yalda

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Abstract

The contribution of rare and low-frequency variants to human traits is largely unexplored. Here we describe insights from sequencing whole genomes (low read depth, 7×) or exomes (high read depth, 80×) of nearly 10,000 individuals from population-based and disease collections. In extensively phenotyped cohorts we characterize over 24 million novel sequence variants, generate a highly accurate imputation reference panel and identify novel alleles associated with levels of triglycerides (APOB), adiponectin (ADIPOQ) and low-density lipoprotein cholesterol (LDLR and RGAG1) from single-marker and rare variant aggregation tests. We describe population structure and functional annotation of rare and low-frequency variants, use the data to estimate the benefits of sequencing for association studies, and summarize lessons from disease-specific collections. Finally, we make available an extensive resource, including individual-level genetic and phenotypic data and web-based tools to facilitate the exploration of association results.

Item Type: Article
Additional Information: This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported licence. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons licence, users will need to obtain permission from the licence holder to reproduce the material. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-sa/3.0.
Keywords: Adiponectin, Alleles, Cohort Studies, Disease, Exome, Female, Genetic Predisposition to Disease, Genetic Variation, Genetics, Medical, Genetics, Population, Genome, Human, Genome-Wide Association Study, Genomics, Health, Humans, Lipid Metabolism, Male, Molecular Sequence Annotation, Receptors, LDL, Reference Standards, Sequence Analysis, DNA, Triglycerides, United Kingdom, UK10K Consortium, Humans, Disease, Genetic Predisposition to Disease, Triglycerides, Receptors, LDL, Cohort Studies, Sequence Analysis, DNA, Genetics, Medical, Genetics, Population, Genomics, Alleles, Genome, Human, Reference Standards, Health, Female, Male, Lipid Metabolism, Adiponectin, Genetic Variation, Genome-Wide Association Study, Molecular Sequence Annotation, Exome, United Kingdom, MD Multidisciplinary, General Science & Technology
SGUL Research Institute / Research Centre: Academic Structure > Institute of Medical & Biomedical Education (IMBE)
Academic Structure > Institute of Medical & Biomedical Education (IMBE) > Centre for Clinical Education (INMECE )
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Academic Structure > Population Health Research Institute (INPH)
Journal or Publication Title: Nature
ISSN: 1476-4687
Language: eng
Dates:
DateEvent
1 October 2015Published
14 September 2015Published Online
17 July 2015Accepted
Projects:
Project IDFunderFunder ID
G0500870Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
104125Wellcome Trusthttp://dx.doi.org/10.13039/100004440
102215Wellcome Trusthttp://dx.doi.org/10.13039/100004440
096599Wellcome Trusthttp://dx.doi.org/10.13039/100004440
MC_U106179472Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
RG/10/17/28553British Heart Foundationhttp://dx.doi.org/10.13039/501100000274
MC_UU_12013/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
MR/K013351/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
RG/10/13/28570British Heart Foundationhttp://dx.doi.org/10.13039/501100000274
MR/L010305/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
PG/07/045/22690British Heart Foundationhttp://dx.doi.org/10.13039/501100000274
RG/08/008/25291British Heart Foundationhttp://dx.doi.org/10.13039/501100000274
MC_UU_12013/3Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
095564Wellcome Trusthttp://dx.doi.org/10.13039/100004440
104036Wellcome Trusthttp://dx.doi.org/10.13039/100004440
MR/J012165/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
SCD/12Chief Scientist Officehttp://dx.doi.org/10.13039/501100000589
MC_UU_12015/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
WT091310Wellcome Trusthttp://dx.doi.org/10.13039/100004440
MC_PC_15018Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
MC_UU_12015/2Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
098498Wellcome Trusthttp://dx.doi.org/10.13039/100004440
MC_UU_12013/4Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
CZD/16/6/4Chief Scientist Officehttp://dx.doi.org/10.13039/501100000589
095515Wellcome Trusthttp://dx.doi.org/10.13039/100004440
G0801843Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
100574Wellcome Trusthttp://dx.doi.org/10.13039/100004440
G0902313Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
100140Wellcome Trusthttp://dx.doi.org/10.13039/100004440
G0800509Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
091551Wellcome Trusthttp://dx.doi.org/10.13039/100004440
PubMed ID: 26367797
Web of Science ID: WOS:000362095100038
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/112983
Publisher's version: https://doi.org/10.1038/nature14962

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