Discovery and refinement of genetic loci associated with cardiometabolic risk using dense imputation maps
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Accepted version
Author(s)
Type
Journal Article
Abstract
Large-scale whole genome sequence datasets offer novel opportunities to identify genetic variation
underlying human traits. Here we apply genotype imputation based on whole genome sequence
data from the UK10K and the 1000 Genomes Projects into 35,981 study participants of European
ancestry, followed by association analysis with twenty quantitative cardiometabolic and
hematologic traits. We describe 17 novel associations, including six rare (minor allele frequency
[MAF]<1%) or low frequency variants (1%<MAF<5%) with platelet count (PLT), red cell indices
(MCH, MCV) and high-density lipoprotein (HDL) cholesterol. Applying fine-mapping analysis to
233 known and novel loci associated with the twenty traits, we resolve associations of 59 loci to
credible sets of 20 or less variants, and describe trait enrichments within regions of predicted
regulatory function. These findings augment understanding of the allelic architecture of risk
factors for cardiometabolic and hematologic diseases, and provide additional functional insights
with the identification of potentially novel biological targets.
underlying human traits. Here we apply genotype imputation based on whole genome sequence
data from the UK10K and the 1000 Genomes Projects into 35,981 study participants of European
ancestry, followed by association analysis with twenty quantitative cardiometabolic and
hematologic traits. We describe 17 novel associations, including six rare (minor allele frequency
[MAF]<1%) or low frequency variants (1%<MAF<5%) with platelet count (PLT), red cell indices
(MCH, MCV) and high-density lipoprotein (HDL) cholesterol. Applying fine-mapping analysis to
233 known and novel loci associated with the twenty traits, we resolve associations of 59 loci to
credible sets of 20 or less variants, and describe trait enrichments within regions of predicted
regulatory function. These findings augment understanding of the allelic architecture of risk
factors for cardiometabolic and hematologic diseases, and provide additional functional insights
with the identification of potentially novel biological targets.
Date Issued
2016-09-26
Date Acceptance
2016-09-01
Citation
Nature Genetics, 2016, 48 (11), pp.1303-1312
ISSN
1061-4036
Publisher
Nature Publishing Group
Start Page
1303
End Page
1312
Journal / Book Title
Nature Genetics
Volume
48
Issue
11
Copyright Statement
© 2016 Nature Publishing Group. All rights reserved.
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000386543400005&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
GENOME-WIDE ASSOCIATION
CAUSES HEREDITARY THROMBOCYTHEMIA
SPLICE DONOR MUTATION
LOW-FREQUENCY
THROMBOPOIETIN GENE
SEQUENCE VARIANTS
RARE VARIANTS
BLOOD-CELL
ANTIPHOSPHOLIPID SYNDROME
SUPER-ENHANCERS
Publication Status
Published