comorbidPGS: An R Package Assessing Shared Predisposition between Phenotypes Using Polygenic Scores.

Introduction: Polygenic score (PGS) is a valuable method for assessing the estimated genetic liability to a given outcome or genetic variability contributing to a quantitative trait. While polygenic risk scores are widely used for complex traits, their application in uncovering shared genetic predisposition between phenotypes, i.e.

Blood DNA methylation profiling identifies cathepsin Z dysregulation in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is characterised by pulmonary vascular remodelling causing premature death from right heart failure. Established DNA variants influence PAH risk, but susceptibility from epigenetic changes is unknown. We addressed this through epigenome-wide association study (EWAS), testing 865,848 CpG sites for association with PAH in 429 individuals with PAH and 1226 controls.

GWAS of random glucose in 476,326 individuals provide insights into diabetes pathophysiology, complications and treatment stratification.

Conventional measurements of fasting and postprandial blood glucose levels investigated in genome-wide association studies (GWAS) cannot capture the effects of DNA variability on 'around the clock' glucoregulatory processes. Here we show that GWAS meta-analysis of glucose measurements under nonstandardized conditions (random glucose (RG)) in 476,326 individuals of diverse ancestries and without diabetes enables locus discovery and innovative pathophysiological observations. We discovered 120 RG loci represented by 150 distinct signals, including 13 with sex-dimorphic effects, two cross-ancestry and seven rare frequency signals.

Bidirectional Mendelian Randomization and Multiphenotype GWAS Show Causality and Shared Pathophysiology Between Depression and Type 2 Diabetes.

Objective: Depression is a common comorbidity of type 2 diabetes. We assessed the causal relationships and shared genetics between them.

Research Design And Methods: We applied two-sample, bidirectional Mendelian randomization (MR) to assess causality between type 2 diabetes and depression.

Abdominal obesity is a more important causal risk factor for pancreatic cancer than overall obesity.

Obesity and type 2 diabetes (T2D) are associated with increased risk of pancreatic cancer. Here we assessed the relationship between pancreatic cancer and two distinct measures of obesity, namely total adiposity, using BMI, versus abdominal adiposity, using BMI adjusted waist-to-hip ratio (WHRadjBMI) by utilising polygenic scores (PGS) and Mendelian randomisation (MR) analyses. We constructed z-score weighted PGS for BMI and WHRadjBMI using publicly available data and tested for their association with pancreatic cancer defined in UK biobank (UKBB).

Maternal and perinatal obesity induce bronchial obstruction and pulmonary hypertension via IL-6-FoxO1-axis in later life.

Obesity is a pre-disposing condition for chronic obstructive pulmonary disease, asthma, and pulmonary arterial hypertension. Accumulating evidence suggests that metabolic influences during development can determine chronic lung diseases (CLD). We demonstrate that maternal obesity causes early metabolic disorder in the offspring.

LongITools: Dynamic longitudinal exposome trajectories in cardiovascular and metabolic noncommunicable diseases.

The current epidemics of cardiovascular and metabolic noncommunicable diseases have emerged alongside dramatic modifications in lifestyle and living environments. These correspond to changes in our "modern" postwar societies globally characterized by rural-to-urban migration, modernization of agricultural practices, and transportation, climate change, and aging. Evidence suggests that these changes are related to each other, although the social and biological mechanisms as well as their interactions have yet to be uncovered.

Supplementation with Iron in Pulmonary Arterial Hypertension. Two Randomized Crossover Trials.

Iron deficiency, in the absence of anemia, is common in patients with idiopathic and heritable pulmonary arterial hypertension (PAH) and is associated with a worse clinical outcome. Oral iron absorption may be impeded by elevated circulating hepcidin concentrations. The safety and benefit of parenteral iron replacement in this patient population is unclear.

Expression Quantitative Trait Locus Mapping in Pulmonary Arterial Hypertension.

Expression quantitative trait loci (eQTL) can provide a link between disease susceptibility variants discovered by genetic association studies and biology. To date, eQTL mapping studies have been primarily conducted in healthy individuals from population-based cohorts. Genetic effects have been known to be context-specific and vary with changing environmental stimuli.

Mendelian randomisation analysis of red cell distribution width in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a rare disease that leads to premature death from right heart failure. It is strongly associated with elevated red cell distribution width (RDW), a correlate of several iron status biomarkers. High RDW values can signal early-stage iron deficiency or iron deficiency anaemia.

Genetic determinants of risk in pulmonary arterial hypertension: international genome-wide association studies and meta-analysis.

Background: Rare genetic variants cause pulmonary arterial hypertension, but the contribution of common genetic variation to disease risk and natural history is poorly characterised. We tested for genome-wide association for pulmonary arterial hypertension in large international cohorts and assessed the contribution of associated regions to outcomes.

Methods: We did two separate genome-wide association studies (GWAS) and a meta-analysis of pulmonary arterial hypertension.

Recent advances in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a rare disorder with a high mortality rate. Treatment options have improved in the last 20 years, but patients still die prematurely of right heart failure. Though rare, it is heterogeneous at the genetic and molecular level, and understanding and exploiting this is key to the development of more effective treatments.

Endovascular therapy for vasospasm after aneurysmatic subarachnoid hemorrhage.

Introduction: Balloon angioplasty and/or selective intra-arterial vasodilator therapies are treatment options in patients with vasospasm after subarachnoid hemorrhage (SAH). We analyzed the effect of balloon angioplasty and/or selective intra-arterial vasodilator therapy in our patients.

Methods: Twenty-six patients (vasodilation group, VDT) were treated with intra-arterial nimodipine.

Identification of proteomic differences between squamous cell carcinoma of the lung and bronchial epithelium.

Proteins that exhibit different expression levels in normal and malignant lung cells are good candidate biomarkers to improve early diagnosis and intervention. We used a quantitative approach and compared the proteome of microdissected cells from normal human bronchial epithelium and squamous cell carcinoma tumors of histopathological grades G2 and G3. DIGE analysis and subsequent MS-based protein identification revealed that 32 non-redundant proteins were differentially regulated between the respective tissue types.