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. 2018 Dec;11(12):e002239.
doi: 10.1161/CIRCGEN.118.002239.

Bivariate Genome-Wide Association Scan Identifies 6 Novel Loci Associated With Lipid Levels and Coronary Artery Disease

Katherine M Siewert  1 , Benjamin F Voight  2   3   4
Affiliations

Bivariate Genome-Wide Association Scan Identifies 6 Novel Loci Associated With Lipid Levels and Coronary Artery Disease

Katherine M Siewert et al. Circ Genom Precis Med. 2018 Dec.

Abstract

Background: Plasma lipid levels are heritable and genetically associated with risk of coronary artery disease (CAD). However, genome-wide association studies (GWAS) routinely analyze these traits independent of one another. Joint GWAS for two related phenotypes can lead to a higher powered analysis to detect variants contributing to both traits.

Methods: We performed a bivariate GWAS to discover novel loci associated with both heart disease, using a CAD meta-analysis (122 733 cases and 424 528 controls), and lipid traits, using results from the Global Lipid Genetics Consortium (188 577 subjects).

Results: We identified six previously unreported loci at genome-wide significance ( P<5×10-8), three which were associated with triglycerides and CAD, two which were associated with LDL (low-density lipoprotein) cholesterol and CAD, and one associated with total cholesterol and CAD. At several of our loci, the GWAS signals jointly localize with genetic variants associated with expression level changes for more than one neighboring genes, indicating that these loci may be affecting disease risk through regulatory activity.

Conclusions: We discovered six novel variants individually associated with both lipids and CAD.

Keywords: coronary artery disease; genomics; heart diseases; lipids; triglycerides.

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Figures

Figure 1:
Figure 1:
GWAS signals for Triglycerides (TG), CAD and T2D at the GCK locus.
Figure 2
Figure 2
GWAS and eQTL associations at the SET1B locus. Triglyceride, HDL-C and CAD signals are the GWAS signal corresponding to the respective traits. eQTL associations are for expression of the gene in Adipose Subcutaneous.
Figure 3:
Figure 3:
GWAS and eQTL Associations at the CORO1C locus. LDL-C and CAD signals are the GWAS signal corresponding to the respective traits. CORO1C eQTL signal is for expression in adipose, and SSH1 is for expression in whole blood.
Figure 4:
Figure 4:
GWAS and eQTL Associations at the FBRSL1 locus. Triglyceride (TG) and CAD signals are the GWAS signal corresponding to the respective traits. FBRSL1 eQTL is signal is for expression of the gene in pancreas.
Figure 5:
Figure 5:
GWAS Associations at the CSK locus. Total Cholesterol (TC), LDL-C and SBP (systolic blood pressure) and CAD signals are the GWAS signal corresponding to the respective traits.
See this image and copyright information in PMC

References

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