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Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction

The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N = 293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified

Early growth response 1 regulates hematopoietic support and proliferation in human primary bone marrow stromal cells

Human bone marrow stromal cells are key elements of the hematopoietic environment and they play a central role in bone and bone marrow physiology. However, how key stromal cell functions are regulated is largely unknown. We analyzed the role of the immediate early response transcription factor EGR1 as key stromal cell regulator and found that EGR1 was highly expressed in prospectively-isolated pri

A nutrient-wide association study for risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition and the Netherlands Cohort Study

Purpose: The evidence from the literature regarding the association of dietary factors and risk of prostate cancer is inconclusive. Methods: A nutrient-wide association study was conducted to systematically and comprehensively evaluate the associations between 92 foods or nutrients and risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC). Cox proportio

Beta-blocker therapy and risk of vascular dementia : A population-based prospective study

There are a few studies that report cognitive impairment as a complication of treatment with beta- blockers. We aimed to evaluate the longitudinal association between use of beta-blockers, as a class, and incident risk of all-cause dementia, vascular dementia, Alzheimer's and mixed dementia in the prospective population-based Malmö Preventive Project. We included 18,063 individuals (mean age 68.2,

Nationwide study of appendicitis in children

Background: Paediatric surgical care is increasingly being centralized away from low-volume centres, and prehospital delay is considered a risk factor for more complicated appendicitis. The aim of this study was to determine the incidence of paediatric appendicitis in Sweden, and to assess whether distance to the hospital was a risk factor for complicated disease. Methods: A nationwide cohort stud

Comment on 'AIRE-deficient patients harbor unique high-affinity disease-ameliorating autoantibodies'

The AIRE gene plays a key role in the development of central immune tolerance by promoting thymic presentation of tissue-specific molecules. Patients with AIRE-deficiency develop multiple autoimmune manifestations and display autoantibodies against the affected tissues. In 2016 it was reported that: i) the spectrum of autoantibodies in patients with AIRE-deficiency is much broader than previously

A biomarker of collagen type I degradation is associated with cardiovascular events and mortality in patients with atherosclerosis

Objective: Atherosclerosis is characterized by accumulation of lipids, cells and extracellular matrix (ECM) proteins in the arterial wall. Collagen type I (COL1), a component of the arterial ECM, is cleaved by matrix metalloproteinases (MMPs) and known to be remodelled in atherosclerosis. We explored whether the MMP-mediated COL1 biomarker, C1M, was associated with cardiovascular events, cardiovas

Predictive Value of High-Sensitivity Troponin T for Systolic Dysfunction and Infarct Size (Six Months) After ST-Elevation Myocardial Infarction

The association of markers of myocardial injury and dysfunction with infarct size (IS) and ejection fraction (EF) are well documented. However, limited data are available on the newer high-sensitivity troponin assays and comparison with morphologic and functional assessment with cardiac magnetic resonance imaging. We aimed to examine the associations of high-sensitivity cardiac Troponin-T (hs-cTnT

Familial Mortality Risks in Patients With Heart Failure : A Swedish Sibling Study

Background The influence of familial factors on the prognosis of heart failure (HF) is unknown. This nationwide follow‐up study aimed to determine familial mortality risks of HF among Swedish siblings hospitalized for HF. Methods and Results We linked several Swedish nationwide registers for individuals aged 0 to 80 years. The study population consisted of 373 people hospitalized for HF for the

Growth differentiation factor 15 is positively associated with incidence of diabetes mellitus : the Malmö Diet and Cancer–Cardiovascular Cohort

Aims/hypothesis: Growth differentiation factor 15 (GDF-15) is an anti-inflammatory cytokine of the transforming growth factor-β superfamily. Circulating levels of GDF-15 are associated with hyperglycaemia among people with obesity or diabetes, but longitudinal evidence on the association between GDF-15 levels and diabetes risk is scarce. Our aim was to explore whether circulating levels of GDF-15

Junctional Adhesion Molecule 2 Represents a Subset of Hematopoietic Stem Cells with Enhanced Potential for T Lymphopoiesis

The distinct lineage potential is a key feature of hematopoietic stem cell (HSC) heterogeneity, but a subset of HSCs specialized for a single lymphoid compartment has not been identified. Here we report that HSCs expressing junctional adhesion molecule 2 (Jam2) at a higher level (Jam2high HSCs) have a greater T cell reconstitution capacity. Jam2high HSCs are metabolically dormant but preferentiall

Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

INTRODUCTION: More than 70 common alleles are known to be involved in breast cancer (BC) susceptibility, and several exhibit significant heterogeneity in their associations with different BC subtypes. Although there are differences in the association patterns between BRCA1 and BRCA2 mutation carriers and the general population for several loci, no study has comprehensively evaluated the associatio

White matter lesions and brain atrophy in systemic lupus erythematosus patients : correlation to cognitive dysfunction in a cohort of systemic lupus erythematosus patients using different definition models for neuropsychiatric systemic lupus erythematosus

Aim: The aim of this study was to evaluate the extent of white matter lesions, atrophy of the hippocampus and corpus callosum, and their correlation with cognitive dysfunction (CD), in patients diagnosed with systemic lupus erythematosus (SLE). Methods: Seventy SLE patients and 25 healthy individuals (HIs) were included in the study. To evaluate the different SLE and neuropsychiatric SLE (NPSLE) d

Genome-wide interaction study of smoking behavior and non-small cell lung cancer risk in Caucasian population

Non-small cell lung cancer is the most common type of lung cancer. Both environmental and genetic risk factors contribute to lung carcinogenesis. We conducted a genome-wide interaction analysis between single nucleotide polymorphisms (SNPs) and smoking status (never- versus ever-smokers) in a European-descent population. We adopted a two-step analysis strategy in the discovery stage: we first cond

Alcohol consumption and risk of urothelial cell bladder cancer in the European prospective investigation into cancer and nutrition cohort

Findings on the association between alcohol consumption and bladder cancer are inconsistent. We investigated that association in the European Prospective Investigation into Cancer and Nutrition cohort. We included 476,160 individuals mostly aged 35–70 years, enrolled in ten countries and followed for 13.9 years on average. Hazard ratios (HR) for developing urothelial cell carcinoma (UCC; 1,802 inc

Claudin-4 expression is associated with progression free survival in ovarian cancer, but not with chemotherapy response

The tight junction protein claudin-4 has been reported to be overexpressed in advanced ovarian cancer. We investigated the prognostic significance of claudin-4 overexpression and whether claudin-4 expression could predict platinum response in primary ovarian carcinoma (OC). Claudin-4 expression was evaluated by immunohistochemistry in a tissue microarray of 140 OCs. Multivariable Cox-regression mo

Critical Modulation of Hematopoietic Lineage Fate by Hepatic Leukemia Factor

A gradual restriction in lineage potential of multipotent stem/progenitor cells is a hallmark of adult hematopoiesis, but the underlying molecular events governing these processes remain incompletely understood. Here, we identified robust expression of the leukemia-associated transcription factor hepatic leukemia factor (Hlf) in normal multipotent hematopoietic progenitors, which was rapidly downr

Genetic variation in the ADIPOQ gene, adiponectin concentrations and risk of colorectal cancer : a Mendelian Randomization analysis using data from three large cohort studies

Higher levels of circulating adiponectin have been related to lower risk of colorectal cancer in several prospective cohort studies, but it remains unclear whether this association may be causal. We aimed to improve causal inference in a Mendelian Randomization meta-analysis using nested case–control studies of the European Prospective Investigation into Cancer and Nutrition (EPIC, 623 cases, 623

Treatment with belimumab in systemic lupus erythematosus does not impair antibody response to 13-valent pneumococcal conjugate vaccine.

Background/purpose: The objective of this study was to explore the impact of systemic lupuserythematosus and belimumab given in addition to standard of care therapy on 13-valentconjugated pneumococcal vaccine (PCV13) response. Methods: Forty-seven systemic lupuserythematosus patients and 21 healthy controls were immunized with a single dose of13-valent conjugated pneumococcal vaccine. Forty system