Web-Based Genome Analysis of Bacterial Meningitis Pathogens for Public Health Applications Using the Bacterial Meningitis Genomic Analysis Platform (BMGAP).

Effective laboratory-based surveillance and public health response to bacterial meningitis depends on timely characterization of bacterial meningitis pathogens. Traditionally, characterizing bacterial meningitis pathogens such as (Nm) and (Hi) required several biochemical and molecular tests. Whole genome sequencing (WGS) has enabled the development of pipelines capable of characterizing the given pathogen with equivalent results to many of the traditional tests.

Hypertrophy-associated polymorphisms ascertained in a founder cohort applied to heart failure risk and mortality.

A three-stage approach was undertaken using genome-wide, case-control, and case-only association studies to identify genetic variants associated with heart failure mortality. In an Amish founder population (n = 851), cardiac hypertrophy, a trait integral to the adaptive response to failure, was found to be heritable (h² = 0.28, p = 0.

Providing context and interpretability to genetic association analysis results using the KGraph.

The KGraph is a data visualization system that has been developed to display the complex relationships between the univariate and bivariate associations among an outcome of interest, a set of covariates, and a set of genetic variations such as single-nucleotide polymorphisms (SNPs). It allows for easy simultaneous viewing and interpretation of genetic associations, correlations among covariates and SNPs, and information about the replication and cross-validation of these associations. The KGraph allows the user to more easily investigate multicollinearity and confounding through visualization of the multidimensional correlation structure underlying genetic associations.

Clinical and genetic modifiers of long-term survival in heart failure.

Objectives: This study sought to identify genetic modifiers of beta-blocker response and long-term survival in heart failure (HF).

Background: Differences in beta-blocker treatment effect between Caucasians and African Americans with HF have been reported.

Methods: This was a prospective cohort study of 2,460 patients (711 African American, 1,749 Caucasian) enrolled between 1999 and 2007; 2,039 patients (81.

Complexity in the genetic architecture of leukoaraiosis in hypertensive sibships from the GENOA Study.

Background: Subcortical white matter hyperintensity on magnetic resonance imaging (MRI) of the brain, referred to as leukoaraiosis, is associated with increased risk of stroke and dementia. Hypertension may contribute to leukoaraiosis by accelerating the process of arteriosclerosis involving penetrating small arteries and arterioles in the brain. Leukoaraiosis volume is highly heritable but shows significant inter-individual variability that is not predicted well by any clinical covariates (except for age) or by single SNPs.

Multiple interactions between the alpha 2C- and beta1-adrenergic receptors influence heart failure survival.

Background: Persistent stimulation of cardiac beta1-adrenergic receptors by endogenous norepinephrine promotes heart failure progression. Polymorphisms of this gene are known to alter receptor function or expression, as are polymorphisms of the alpha 2C-adrenergic receptor, which regulates norepinephrine release from cardiac presynaptic nerves. The purpose of this study was to investigate possible synergistic effects of polymorphisms of these two intronless genes (ADRB1 and ADRA2C, respectively) on the risk of death/transplant in heart failure patients.

A GRK5 polymorphism that inhibits beta-adrenergic receptor signaling is protective in heart failure.

Beta-adrenergic receptor (betaAR) blockade is a standard therapy for cardiac failure and ischemia. G protein-coupled receptor kinases (GRKs) desensitize betaARs, suggesting that genetic GRK variants might modify outcomes in these syndromes. Re-sequencing of GRK2 and GRK5 revealed a nonsynonymous polymorphism of GRK5, common in African Americans, in which leucine is substituted for glutamine at position 41.

The genetic architecture of fasting plasma triglyceride response to fenofibrate treatment.

Metabolic response to the triglyceride (TG)-lowering drug, fenofibrate, is shaped by interactions between genetic and environmental factors, yet knowledge regarding the genetic determinants of this response is primarily limited to single-gene effects. Since very low-density lipoprotein (VLDL) is the central carrier of fasting TG, identifying factors that affect both total TG and VLDL-TG response to fenofibrate is critical for predicting individual fenofibrate response. As part of the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study, 688 individuals from 161 families were genotyped for 91 single-nucleotide polymorphisms (SNPs) in 25 genes known to be involved in lipoprotein metabolism.

A functional polymorphism of the Galphaq (GNAQ) gene is associated with accelerated mortality in African-American heart failure.

Galphaq, encoded by the human GNAQ gene, is an effector subunit of the Gq heterotrimeric G-protein and the convergence point for signaling of multiple Gq-coupled neurohormonal receptors. To identify naturally occurring mutations that could modify GNAQ transcription, we examined genomic DNA isolated from 355 normal subjects for genetic variants in transcription factor binding motifs. Of seven variants identified, the most common was a GC to TT dinucleotide substitution at -694/-695 (allele frequency of 0.

KGraph: a system for visualizing and evaluating complex genetic associations.

Unlabelled: The KGraph is a data visualization system that has been developed to display the complex relationships between the univariate and bivariate associations among an outcome of interest, a set of covariates, and a set of genetic factors, such as single nucleotide polymorphisms (SNPs). It allows for easy viewing and interpretation of genetic associations, correlations among covariates and SNPs, and information about the replication and cross-validation of the associations. The KGraph allows the user to more easily investigate multicollinearity and confounding through visualization of the multidimensional correlation structure underlying genetic associations.