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The UK10K project identifies rare variants in health and disease.

Published version
Peer-reviewed

Type

Article

Change log

Authors

UK10K Consortium 
Walter, Klaudia 
Min, Josine L 
Huang, Jie 
Crooks, Lucy 

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.

Description

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

Journal Title

Nature

Conference Name

Journal ISSN

0028-0836
1476-4687

Volume Title

526

Publisher

Springer Science and Business Media LLC
Sponsorship
Medical Research Council (MC_UU_12015/2)
Medical Research Council (MC_UU_12015/1)
MRC (MC_PC_13046)
MRC (MC_PC_13048)
Medical Research Council (MC_UU_12012/5/B)
Wellcome Trust (095515/Z/11/Z)
Wellcome Trust (100574/Z/12/Z)
Wellcome Trust (100140/Z/12/Z)
Wellcome Trust (098498/Z/12/Z)
Wellcome Trust (095564/Z/11/Z)
Wellcome Trust (091551/Z/10/A)
Wellcome Trust (091310/Z/10/Z)
Medical Research Council (MC_U106179472)
Wellcome Trust (100585/Z/12/Z)
TCC (None)
Medical Research Council (MC_UU_12012/5)
Medical Research Council (MC_PC_12012)
Medical Research Council (MC_PC_13048)
Medical Research Council (MC_PC_13046)