The impact of low-frequency and rare variants on lipid levels
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
Using a genome-wide screen of 9.6 million genetic variants achieved through 1000 Genomes Project imputation in 62,166 samples, we identify association to lipid traits in 93 loci, including 79 previously identified loci with new lead SNPs and 10 new loci, 15 loci with a low-frequency lead SNP and 10 loci with a missense lead SNP, and 2 loci with an accumulation of rare variants. In six loci, SNPs with established function in lipid genetics (CELSR2, GCKR, LIPC and APOE) or candidate missense mutations with predicted damaging function (CD300LG and TM6SF2) explained the locus associations. The low-frequency variants increased the proportion of variance explained, particularly for low-density lipoprotein cholesterol and total cholesterol. Altogether, our results highlight the impact of low-frequency variants in complex traits and show that imputation offers a cost-effective alternative to resequencing.
Date Issued
2015-05-11
Date Acceptance
2015-04-16
Citation
Nature Genetics, 2015, 47 (6), pp.589-597
ISSN
1061-4036
Publisher
Nature Publishing Group
Start Page
589
End Page
597
Journal / Book Title
Nature Genetics
Volume
47
Issue
6
Copyright Statement
© 2015 Nature America, Inc. All rights reserved.
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000355386500009&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
GENOME-WIDE ASSOCIATION
HETEROGENEITY
EXPRESSION
SIALOMUCIN
SEQUENCE
GLUCOSE
GENES
CD300
LOCI
Dyslipidemias
Gene Frequency
Genetic Loci
Genome-Wide Association Study
Humans
Linkage Disequilibrium
Lipid Metabolism
Mutation, Missense
Polymorphism, Single Nucleotide
Sequence Analysis, DNA
ENGAGE Consortium
Humans
Sequence Analysis, DNA
Gene Frequency
Linkage Disequilibrium
Mutation, Missense
Polymorphism, Single Nucleotide
Dyslipidemias
Lipid Metabolism
Genome-Wide Association Study
Genetic Loci
06 Biological Sciences
11 Medical and Health Sciences
Developmental Biology
Publication Status
Published
Date Publish Online
2015-05-11