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Raised blood pressure (BP) is a major risk factor for cardiovascular disease. Previous studies have identified 47 distinct genetic variants robustly associated with BP, but collectively these explain only a few percent of the heritability for BP phenotypes. To find additional BP loci, we used a bespoke gene-centric array to genotype an independent discovery sample of 25,118 individuals that combin
-Despite recent discoveries of new genetic risk factors, the majority of risk for coronary artery disease (CAD) remains elusive. As the most proximal sensor of DNA variation, RNA abundance can help identify subpopulations of genetic variants active in and across tissues mediating CAD risk through gene expression.
Coronary heart disease (CHD) is an archetypical multifactorial disorder that is influenced by genetic susceptibility as well as both modifiable and nonmodifiable risk factors, and their interactions. Advances during recent years in the field of multifactorial genetics, in particular genomewide association studies (GWASs) and their meta-analyses, have provided the statistical power to identify and
Increased PDGFRA signaling is an essential pathogenic factor in many subtypes of gliomas. In this context the cell surface expression of PDGFRA is an important determinant of ligand sensing in the glioma microenvironment. However, the regulation of spatial distribution of PDGFRA in glioma cells remains poorly characterized. Here, we report that cell surface PDGFRA expression in gliomas is negative
Objective. Lack of adherence with pharmacological therapy is a public health concern that compels tremendous costs for the health care system and the community. To analyse the association between socioeconomic disadvantage and primary nonadherence with medication, and to explore possible mediating effects of trust in health care and lifestyle profile. Design. Cross-sectional population-based study
The aim of the study was to investigate the resting levels of novel cardiovascular biomarkers in common types of noncardiac syncope.
From histopathological specimens, endolymphatic hydrops has been demonstrated in association with inner ear disorders. Recent studies have observed findings suggestive of hydrops using MRI in humans. Previous studies suggest that vasopressin may play a critical role in endolymph homeostasis and may be involved in the development of Ménière's disease. In this study we evaluate the effect of vasopre
Non-alcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease in Western countries. Diagnosis of NASH requires a liver biopsy. We estimated the prevalence of NASH non-invasively in a population-based study using scores validated against liver histology.
We sought to identify novel pharmacogenetic markers associated with cardiovascular outcomes in patients with hypertension on antihypertensive therapy. We genotyped a 1:4 case:control cohort (n=1345) on the Illumina HumanCVD Beadchip from the INternational VErapamil SR-Trandolapril STudy (INVEST), where participants were randomized to a -blocker strategy or a calcium channel blocker strategy. Genom
The locus encompassing the corticosteroidogenic genes CYP11B2 and CYP11B1 is of potential importance in essential hypertension. We analyzed the association of polymorphisms at this locus with risk of essential hypertension, using 2 white case-control collections for discovery (n = 3340) and confirmation (n = 2929). Single-marker and haplotype analyses were performed, with the CYP11B2 Intron 2 Conv
One of the outstanding challenges presented by liquid water is to understand how molecules can move on a picosecond time scale despite being incorporated in a three-dimensional network of relatively strong H-bonds. This challenge is exacerbated in the supercooled state, where the dramatic slowing down of structural dynamics is reminiscent of the, equally poorly understood, generic behavior of liqu
Background-eQTL analyses are important to improve the understanding of genetic association results. We performed a genome-wide association and global gene expression study to identify functionally relevant variants affecting the risk of coronary artery disease (CAD). Methods and Results-In a genome-wide association analysis of 2078 CAD cases and 2953 control subjects, we identified 950 single-nucl
Background & Aims: The robust association between non-alcoholic fatty liver disease (NAFLD) and the genetic variant I148M (rs738409) in PNPLA3 has been widely replicated. The aim of this study was to investigate the effect of the PNPLA3 I148M mutation on: (1) hepatic secretion of very low density lipoproteins (VLDL) in humans; and (2) secretion of apolipoprotein B (apoB) from McA-RH 7777 cells
AIM: Clinical studies have suggested a role for dietary glycaemic index (GI) in body weight regulation and diabetes risk. Here, we investigated the long-term metabolic effects of low and high glycaemic diets using the C57BL/6J mouse model. METHODS: Female C57BL/6J mice were fed low or high glycaemic starch in either low-fat or medium-fat diets for 22 weeks. Oral and intravenous glucose tolerance t
Background-After age, sex is the most important risk factor for coronary artery disease (CAD). The mechanism through which women are protected from CAD is still largely unknown, but the observed sex difference suggests the involvement of the reproductive steroid hormone signaling system. Genetic association studies of the gene-encoding Estrogen Receptor alpha (ESR1) have shown conflicting results,
Objectives We sought to replicate the association between the kinesin-like protein 6 (KIF6) Trp719Arg polymorphism (rs20455), and clinical coronary artery disease (CAD). Background Recent prospective studies suggest that carriers of the 719Arg allele in KIF6 are at increased risk of clinical CAD compared with noncarriers. Methods The KIF6 Trp719Arg polymorphism (rs20455) was genotyped in 19 case-c
To identify genetic factors contributing to type 2 diabetes (T2D), we performed large-scale meta-analyses by using a custom similar to 50,000 SNP genotyping array (the ITMAT-Broad-CARe array) with similar to 2000 candidate genes in 39 multiethnic population-based studies, case-control studies, and clinical trials totaling 17,418 cases and 70,298 controls. First, meta-analysis of 25 studies compris
We prospectively investigated dietary flavonoid intake and esophageal cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The study included 477,312 adult subjects from 10 European countries. At baseline, country-specific validated dietary questionnaires were used. During a mean follow-up of 11 years (1992-2010), there were 341 incident esophageal cancer
As models for β-cell metabolism, rat islets are, to some extent, a, heterogeneous cell-population stressed by the islet isolation procedure, while rat-derived clonal β-cells exhibit a tumor-like phenotype. To describe to what extent either of these models reflect normal cellular metabolism, we compared metabolite profiles and gene expression in rat islets and the INS-1 832/13 line, a widely used c
