Search results

Objective: To implement a mendelian randomization (MR) approach to determine whether type 2 diabetes mellitus (T2D), fasting glucose, fasting insulin, and body mass index (BMI) are causally associated with specific ischemic stroke subtypes. Methods: MR estimates of the association between each possible risk factor and ischemic stroke subtypes were calculated with inverse-variance weighted (convent

Objectives To study the association between lifestyle risk factors and chronic hypertension by history of hypertensive disorders of pregnancy (HDP: gestational hypertension and pre-eclampsia) and investigate the extent to which these risk factors modify the association between HDP and chronic hypertension. Design Prospective cohort study. Setting Nurses' Health Study II (1991-2013). Participants 5

BACKGROUND Clonal hematopoiesis of indeterminate potential (CHIP), which is defined as the presence of an expanded somatic blood-cell clone in persons without other hematologic abnormalities, is common among older persons and is associated with an increased risk of hematologic cancer. We previously found preliminary evidence for an association between CHIP and atherosclerotic cardiovascular diseas

Background and aims After assessing the risk for cardiovascular disease (CVD) based on traditional risk factors, decisions concerning lipid lowering therapy might remain uncertain. To investigate whether lipoprotein subfraction levels could aid these decisions, we assessed the association between lipoprotein subfractions and CVD, after adjustment for traditional risk factors including standard lip

Hand grip strength is a widely used proxy of muscular fitness, a marker of frailty, and predictor of a range of morbidities and all-cause mortality. To investigate the genetic determinants of variation in grip strength, we perform a large-scale genetic discovery analysis in a combined sample of 195,180 individuals and identify 16 loci associated with grip strength (P<5 × 10-8) in combined analyses

Phenotypic variance heterogeneity across genotypes at a single nucleotide polymorphism (SNP) may reflect underlying gene-environment (G×E) or gene-gene interactions. We modeled variance heterogeneity for blood lipids and BMI in up to 44,211 participants and investigated relationships between variance effects (Pv), G×E interaction effects (with smoking and physical activity), and marginal genetic e

Obesity is a genetically heterogeneous disorder. Using targeted and whole-exome sequencing, we studied 32 human and 87 rodent obesity genes in 2,548 severely obese children and 1,117 controls. We identified 52 variants contributing to obesity in 2% of cases including multiple novel variants in GNAS, which were sometimes found with accelerated growth rather than short stature as described previousl

Background: Since the introduction of high-sensitivity troponin assays a greater proportion of atrial fibrillation (AF) patients present with dynamic troponin elevations. We hypothesize that significant coronary artery disease (CAD) causes relative ischemia in the setting of a rapid heart rate resulting in dynamic troponin elevation. The aim of this study was to examine if patients without known C

Aims: Type 2 diabetes is associated with cardiovascular complications. It is largely unknown which patients have poor treatment response and high complication risk; biomarkers are studied for this purpose. The aim of the study was to investigate the association between clinical factors such as HbA1c, level of biomarkers (C-peptide, copeptin) at diagnosis and changes in HbA1c, blood pressure or bod

OBJECTIVE: To assess the effect of the FTO genotype on weight loss after dietary, physical activity, or drug based interventions in randomised controlled trials.DESIGN: Systematic review and random effects meta-analysis of individual participant data from randomised controlled trials.DATA SOURCES: Ovid Medline, Scopus, Embase, and Cochrane from inception to November 2015.ELIGIBILITY CRITERIA FOR S

oxLDL peptide vaccine and its antibody adoptive transferring have shown a significantly preventive or therapeutic effect in atherosclerotic animal model. The molecular mechanism behind this is obscure. Here, we report that oxLDL induces MCP-1 release in monocytes/macrophages through their TLR-4 (Toll-like receptor 4) and ERK MAPK pathway and is calcium/potassium channel-dependent. Using blocking a

The totality of microbial genomes in the gut exceeds the size of the human genome, having around 500-fold more genes that importantly complement our coding potential. Microbial genes are essential for key metabolic processes, such as the breakdown of indigestible dietary fibres to short-chain fatty acids, biosynthesis of amino acids and vitamins, and production of neurotransmitters and hormones. D

BACKGROUND: Right ventricular (RV) dysfunction may be caused by either pressure or volume overload. RV function is conventionally assessed with echocardiography using tricuspid annular plane systolic excursion (TAPSE), RV fractional area change (RVFAC), tricuspid lateral annular systolic velocity (S') and RV index of myocardial performance (RIMP). The purpose of this study was to evaluate whether

Unbiased, “nontargeted” metabolite profiling techniques hold considerable promise for biomarker and pathway discovery, in spite of the lack of successful applications to human disease. By integrating nontargeted metabolomics, genetics, and detailed human phenotyping, we identified dimethylguanidino valeric acid (DMGV) as an independent biomarker of CT-defined nonalcoholic fatty liver disease (NAFL

Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) <5%) coding variants asso

Aims/hypothesis: There is considerable variability in how diabetes progresses after diagnosis. Progression modelling has largely focused on ‘time to failure’ methods, yet determining a ‘coefficient of failure’ has many advantages. We derived a rate of glycaemic deterioration in type 2 diabetes, using a large real-world cohort, and aimed to investigate the clinical, biochemical, pharmacological and

Background: Circulating levels of TNF alpha receptor 1 (TNFR1) and 2 (TNFR2) are associated with increased long-term mortality and impaired kidney function. Aim: To study association between circulating levels of TNFR1 and TNFR2 and short-term mortality in patients with diabetes and dyspnea. Population and methods: Patients aged ≥ 18 years seeking at emergency department (ED) during daytime on wee

Background & Aims: The I148M variant in PNPLA3 is the major genetic risk factor for non-alcoholic fatty liver disease (NAFLD). The liver is enriched with polyunsaturated triglycerides (PUFA-TGs) in PNPLA3-I148M carriers. Gene expression data indicate that PNPLA3 is liver-specific in humans, but whether it functions in adipose tissue (AT) is unknown. We investigated whether PNPLA3-I148M modifie

Arterial stiffening is a hallmark of early vascular aging (EVA) syndrome and an independent predictor of cardiovascular morbidity and mortality. In this case-control study we sought to identify plasma metabolites associated with EVA syndrome in the setting of hypertension. An untargeted metabolomic approach was used to identify plasma metabolites in an age-, BMI-, and sex-matched groups of EVA (n