Meta-analysis of 49 549 individuals imputed with the 1000 Genomes Project reveals an exonic damaging variant in ANGPTL4 determining fasting TG levels
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Published version
Author(s)
Type
Journal Article
Abstract
BACKGROUND: So far, more than 170 loci have been associated with circulating lipid levels through genome-wide association studies (GWAS). These associations are largely driven by common variants, their function is often not known, and many are likely to be markers for the causal variants. In this study we aimed to identify more new rare and low-frequency functional variants associated with circulating lipid levels. METHODS: We used the 1000 Genomes Project as a reference panel for the imputations of GWAS data from ∼60 000 individuals in the discovery stage and ∼90 000 samples in the replication stage. RESULTS: Our study resulted in the identification of five new associations with circulating lipid levels at four loci. All four loci are within genes that can be linked biologically to lipid metabolism. One of the variants, rs116843064, is a damaging missense variant within the ANGPTL4 gene. CONCLUSIONS: This study illustrates that GWAS with high-scale imputation may still help us unravel the biological mechanism behind circulating lipid levels.
Date Issued
2016-04-01
Date Acceptance
2015-11-23
Citation
Journal of Medical Genetics, 2016, 53, pp.441-449
ISSN
1468-6244
Publisher
BMJ Publishing Group
Start Page
441
End Page
449
Journal / Book Title
Journal of Medical Genetics
Volume
53
Copyright Statement
This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Identifier
PII: jmedgenet-2015-103439
Subjects
Complex traits
Epidemiology
Genetics
Genome-wide
circulating lipid levels
LifeLines Cohort Study
Genetics & Heredity
06 Biological Sciences
11 Medical And Health Sciences
Publication Status
Published