The UK10K project identifies rare variants in health and disease
File(s)
Published version
Author(s)
Type
Journal Article
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.
Date Issued
2015-09-14
Date Acceptance
2015-07-17
Citation
Nature, 2015, 526 (7571), pp.82-90
ISSN
0028-0836
Publisher
Nature Publishing Group
Start Page
82
End Page
90
Journal / Book Title
Nature
Volume
526
Issue
7571
Copyright Statement
This work is licensed under a Creative Commons AttributionNonCommercial-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
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
GENOME-WIDE ASSOCIATION
OF-FUNCTION MUTATIONS
LOW-FREQUENCY
INCIDENTAL FINDINGS
SEQUENCE VARIATION
COMPLEX TRAITS
POPULATION
COMMON
HERITABILITY
APOC3
Adiponectin
Alleles
Cohort Studies
Disease
Exome
Female
Genetic Predisposition to Disease
Genetic Variation
Genetics, Medical
Genetics, Population
Genome, Human
Genome-Wide Association Study
Genomics
Great Britain
Health
Humans
Lipid Metabolism
Male
Molecular Sequence Annotation
Receptors, LDL
Reference Standards
Sequence Analysis, DNA
Triglycerides
UK10K Consortium
General Science & Technology
MD Multidisciplinary
Publication Status
Published