Genetic Profiling Using Genome-Wide Significant Coronary Artery Disease Risk Variants Does Not Improve the Prediction of Subclinical Atherosclerosis: The Cardiovascular Risk in Young Finns Study, the Bogalusa Heart Study and the Health 2000 Survey – A Meta-Analysis of Three Independent Studies

Abstract The functional properties of the apolipoproteins (apoB and apoA-I) governing lipoprotein metabolism make these variables conceptually important as markers for coronary artery disease risk. This aspect was examined in a biracial (black-white) population of children as part of the Bogalusa Heart Study. White children, especially boys, showed lower concentrations of apoA-I and ratios of cholesterol to apoB within low-density lipoprotein (LDL) than did black children. Persistence of apoB concentrations over time, coupled with its strong linkage with apoB gene locus, underscores the value of detecting apoB excess early in life. Further, the impact of apoE genotypes on apoB and apoA-I levels is already evident in childhood. We found that, as a screening test for detecting increased LDL cholesterol, apoB is superior to total cholesterol. Low values for apoA-I concentration, the apoA-I to apoB ratio, and LDL cholesterol to apoB ratio in children are strongly related to parental incidence of myocardial infarction; no such relationship is seen with respect to lipoprotein cholesterols. Thus, expanding screening strategies might be useful for identifying individuals with adverse apolipoprotein profiles early in life.

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Bivariate GWAS scan identifies six novel loci associated with lipid levels and coronary artery disease

10.1101/319848 ◽

2018 ◽

Author(s):

Katherine M. Siewert ◽

Benjamin F. Voight

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Disease Risk ◽

Association Studies ◽

Meta Analysis ◽

Plasma Lipid ◽

Genome Wide Association Studies ◽

Lipid Levels ◽

Genome Wide ◽

Artery Disease

AbstractBackgroundPlasma lipid levels are heritable and genetically associated with risk of coronary artery disease (CAD). However, genome-wide association studies (GWAS) routinely analyze these traits independently of one another. Joint GWAS for two related phenotypes can lead to a higher-powered analysis to detect variants contributing to both traits.Methods and ResultsWe performed a bivariate GWAS to discover novel loci associated with heart disease, using a CAD Meta-Analysis (122,733 cases and 424,528 controls), and lipid traits, using data from the Global Lipid Genetics Consortium (188,577 subjects). 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 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 one or more neighboring genes, indicating that these loci may be affecting disease risk through regulatory activity.ConclusionsWe discovered six novel variants individually associated with both lipids and coronary artery disease.

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