Circulation. Cardiovascular genetics
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Circ Cardiovasc Genet · Apr 2015
Multicenter Study Clinical TrialMultiethnic genome-wide association study of cerebral white matter hyperintensities on MRI.
The burden of cerebral white matter hyperintensities (WMH) is associated with an increased risk of stroke, dementia, and death. WMH are highly heritable, but their genetic underpinnings are incompletely characterized. To identify novel genetic variants influencing WMH burden, we conducted a meta-analysis of multiethnic genome-wide association studies. ⋯ We identified 4 novel genetic loci that implicate inflammatory and glial proliferative pathways in the development of WMH in addition to previously proposed ischemic mechanisms.
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Circ Cardiovasc Genet · Feb 2015
ReviewDoes our gut microbiome predict cardiovascular risk? A review of the evidence from metabolomics.
Millions of microbes are found in the human gut, and are collectively referred as the gut microbiota. Recent studies have estimated that the microbiota genome contains 100-fold more genes than the host genome. These microbiota contribute to digestion by processing energy substrates unutilized by the host, with about half of the total genome of the gut microbiota being related to central carbon and amino acid metabolism as well as the biosynthesis of secondary metabolites. ⋯ Metabolomics is uniquely suited to capture these functional host-microbe interactions. This review aims at providing an overview of recent metabolomics evidence of gut microbiota-host metabolic interactions with a specific focus on cardiovascular disease and related aspects of the metabolic syndrome. Furthermore, the emphasis is given on the complexities of translating these metabolite signatures as potential clinical biomarkers, as the composition and activity of gut microbiome change with many factors, particularly with diet, with special reference to trimethylamine-oxide.
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Circ Cardiovasc Genet · Oct 2014
Meta AnalysisMultiple associated variants increase the heritability explained for plasma lipids and coronary artery disease.
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. ⋯ These results demonstrate that a portion of the missing heritability for lipid traits and CAD can be explained by multiple variants at each locus.
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Circ Cardiovasc Genet · Oct 2014
G protein-coupled receptor kinase 5 gene polymorphisms are associated with postoperative atrial fibrillation after coronary artery bypass grafting in patients receiving β-blockers.
We hypothesized that genetic variations in the adrenergic signaling pathway and cytochrome P450 2D6 enzyme are associated with new-onset atrial fibrillation (AF) in patients who underwent coronary artery bypass grafting and were treated with perioperative β-blockers (BBs). ⋯ In patients undergoing coronary artery bypass grafting, genetic variation in GRK5 is associated with postoperative AF despite perioperative BB therapy.
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Circ Cardiovasc Genet · Oct 2014
Adrenomedullin and arterial stiffness: integrative approach combining monocyte ADM expression, plasma MR-Pro-ADM, and genome-wide association study.
Adrenomedullin (ADM) is a circulating vasoactive peptide involved in vascular homeostasis and endothelial function. Single nucleotide polymorphisms of the ADM gene are associated with blood pressure variability, and elevated levels of plasma midregional proadrenomedullin (MR-pro-ADM) are associated with cardiovascular diseases. ⋯ These results support an involvement of the ADM gene in the modulation of peripheral vascular tone.