Multiple associated variants increase the heritability explained for plasma lipids and coronary artery disease

Tada, Hayato, Won, Hong-Hee, Melander, Olle, Yang, Jian, Peloso, Gina M. and Kathiresan, Sekar (2014) Multiple associated variants increase the heritability explained for plasma lipids and coronary artery disease. Circulation-Cardiovascular Genetics, 7 5: 583-587. doi:10.1161/CIRCGENETICS.113.000420

Attached Files (Some files may be inaccessible until you login with your UQ eSpace credentials)
Name Description MIMEType Size Downloads

Author Tada, Hayato
Won, Hong-Hee
Melander, Olle
Yang, Jian
Peloso, Gina M.
Kathiresan, Sekar
Title Multiple associated variants increase the heritability explained for plasma lipids and coronary artery disease
Journal name Circulation-Cardiovascular Genetics   Check publisher's open access policy
ISSN 1942-325X
Publication date 2014-10
Year available 2014
Sub-type Article (original research)
DOI 10.1161/CIRCGENETICS.113.000420
Open Access Status
Volume 7
Issue 5
Start page 583
End page 587
Total pages 5
Place of publication Dallas, United States
Publisher American Heart Association
Collection year 2015
Language eng
Formatted abstract
Background—Plasma lipid levels as well as coronary artery disease (CAD) have been shown to be highly heritable with estimates ranging from 40% to 60%. However, top variants detected by large-scale genome-wide association studies explain only a fraction of the total variance in plasma lipid phenotypes and CAD.

Methods and Results—We performed a conditional and joint association analysis using summary-level statistics from 2 large genome-wide association meta-analyses: the Global Lipids Genetics Consortium (GLGC) study, and the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) study. There were 100 184 individuals from 46 GLGC studies for plasma lipids, and 22 233 cases and 64 762 controls from 14 studies for CAD. We detected several loci where multiple independent single-nucleotide polymorphisms were associated with lipid traits within a locus (12 out of 33 loci for high-density lipoprotein cholesterol, 10 of 35 loci for low-density lipoprotein cholesterol, 13 of 44 loci for total cholesterol, and 8 of 28 loci for triglycerides), reaching genome-wide significance (P<5×10−8), nearly doubling the heritability explained by genome-wide association studies (from 3.6 to 7.6% for high-density lipoprotein cholesterol, from 5.0 to 8.8% for low-density lipoprotein cholesterol, from 5.5 to 8.8% for total cholesterol, and from 5.7 to 8.5% for triglycerides). Multiple single-nucleotide polymorphisms were also associated with CAD (3 of 15 loci; an increase from 9.6% to 11.4% of heritability explained).

Conclusions—These results demonstrate that a portion of the missing heritability for lipid traits and CAD can be explained by multiple variants at each locus.
Keyword Coronary artery disease
Genome-wide association study
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2015 Collection
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 5 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 5 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Fri, 26 Dec 2014, 19:15:27 EST by System User on behalf of Queensland Brain Institute