Polygenic risk score-based phenome-wide association study identifies novel associations for Tourette syndrome.

Tourette Syndrome (TS) is a complex neurodevelopmental disorder characterized by vocal and motor tics lasting more than a year. It is highly polygenic in nature with both rare and common previously associated variants. Epidemiological studies have shown TS to be correlated with other phenotypes, but large-scale phenome wide analyses in biobank level data have not been performed to date.

Variants in clock genes could be associated with lower risk of type 2 diabetes in an elderly Greek population.

Objectives: Recent evidence has linked circadian rhythm dysregulation to an increased risk of metabolic disorders. This study explores a potential association between variation in genes regulating the endogenous circadian timing system (clock genes) and the risk of type 2 diabetes (T2D) in a sample of Greek elderly people.

Study Design: Variants within and upstream or downstream of PPARA, PPARD, CLOCK/TMEM165, PER1, PER2 and PER3 genes were genotyped in 716 individuals with T2D (A) and 569 normoglycemic controls (B), and allele frequencies were compared between the groups in a case control study design.

Oxidative Stress Genes in Diabetes Mellitus Type 2: Association with Diabetic Kidney Disease.

Diabetic type 2 patients compared to nondiabetic patients exhibit an increased risk of developing diabetic kidney disease (DKD), the leading cause of end-stage renal disease. Hyperglycemia, hypertension, oxidative stress (OS), and genetic background are some of the mechanisms and pathways implicated in DKD pathogenesis. However, data on OS pathway susceptibility genes show limited success and conflicting or inconclusive results.

Myasthenia gravis genome-wide association study implicates AGRN as a risk locus.

Background: Myasthenia gravis (MG) is a rare autoimmune disorder affecting the neuromuscular junction (NMJ). Here, we investigate the genetic architecture of MG via a genome-wide association study (GWAS) of the largest MG data set analysed to date.

Methods: We performed GWAS meta-analysis integrating three different data sets (total of 1401 cases and 3508 controls).

The Polygenic Nature and Complex Genetic Architecture of Specific Learning Disorder.

Specific Learning Disorder (SLD) is a multifactorial, neurodevelopmental disorder which may involve persistent difficulties in reading (dyslexia), written expression and/or mathematics. Dyslexia is characterized by difficulties with speed and accuracy of word reading, deficient decoding abilities, and poor spelling. Several studies from different, but complementary, scientific disciplines have investigated possible causal/risk factors for SLD.

Clinical Profiles and Socio-Demographic Characteristics of Adults with Specific Learning Disorder in Northern Greece.

The manifestation of Specific Learning Disorder (SLD) during adulthood is one of the least examined research areas among the relevant literature. Therefore, the adult population with SLD is considered a "rare" and "unique" population of major scientific interest. The aim of the current study was to investigate, describe, and analyze the clinical, academic, and socio-demographic characteristics, and other everyday functioning life-skills of adults with SLD, in an attempt to shed more light on this limited field of research.

Association of rs11780592 Polymorphism in the Human Soluble Epoxide Hydrolase Gene (EPHX2) with Oxidized LDL and Mortality in Patients with Diabetic Chronic Kidney Disease.

Soluble epoxide hydrolase 2 (EPHX2) is an enzyme promoting increased cellular apoptosis through induction of oxidative stress (OS) and inflammation. The gene which encodes soluble EPHX2 might be implicated in the pathogenesis and development of OS and atherosclerosis. We aimed to assess the possible association between two functional polymorphisms of the gene (rs2741335 and rs11780592) with oxidized LDL (ox-LDL), carotid atherosclerosis, mortality, and cardiovascular (CV) disease in 118 patients with diabetic chronic kidney disease (CKD).

Genetic variation in , a gene coding for an NLRP3 inflammasome-associated protein, alters the genetic risk for diabetic nephropathy in the context of type 2 diabetes mellitus.

Background: Approximately one third of type 2 diabetes mellitus (T2DM) cases present with diabetic nephropathy (DN), the leading cause of end-stage renal disease. Inflammation plays an important role in T2DM disease and DN pathogenesis. NLRP3 inflammasomes are complexes that regulate interleukin-1B (IL-1B) and IL-18 secretion, both involved in inflammatory responses.

Association between CUBN gene variants, type 2 diabetes and vitamin D concentrations in an elderly Greek population.

Accumulating evidence suggests a potential implication of vitamin D biological network in the pathogenesis of diabetes mellitus. The megalin-cubilin endocytotic system constitutes a key transport structure, with a modulating role in vitamin D metabolism. We aimed to assess the contribution of variants in the CUBN gene to the genetic risk of Type 2 Diabetes Mellitus (T2DM).

Neuropathology-driven Whole-genome Sequencing Study Points to Novel Candidate Genes for Healthy Brain Aging.

Purpose: Understanding the healthy brain aging process is key to uncover the mechanisms that lead to pathologic age-related neurodegeneration, including progression to Alzheimer disease (AD). We aimed to address the issue of pathologic heterogeneity that often underlies a clinical AD diagnosis.

Methods: We performed a deep whole-genome sequencing study aiming to identify variants that are associated specifically with healthy brain aging.

European Multicentre Tics in Children Studies (EMTICS): protocol for two cohort studies to assess risk factors for tic onset and exacerbation in children and adolescents.

Genetic predisposition, autoimmunity and environmental factors [e.g. pre- and perinatal difficulties, Group A Streptococcal (GAS) and other infections, stress-inducing events] might interact to create a neurobiological vulnerability to the development of tics and associated behaviours.

Assessment of association between lipoxygenase genes variants in elderly Greek population and type 2 diabetes mellitus.

Background: Inflammation plays a pivotal role in the pathogenesis of diabetes and its complications. Arachidonic acid lipoxygenases have been intensively studied in their role in inflammation in metabolic pathways. Thus, we aimed to explore variants of lipoxygenase genes (arachidonate lipoxygenase genes) in a diabetes adult population using a case-control study design.

Association of ALOX12 gene polymorphism with all-cause and cardiovascular mortality in diabetic nephropathy.

Purpose: Cardiovascular (CV) events are the first cause of death in patients with chronic renal disease (CKD) and in patients with type 2 diabetes mellitus (DM2). The combination of CKD and DM2 elevates the risk of both cardiovascular disease (CVD) and death in this high-risk population. Besides traditional risk factors, such as dyslipidemia, smoking, obesity, and carotid atherosclerosis, novel factors are under investigation such as genetic polymorphisms.

Variant Ranker: a web-tool to rank genomic data according to functional significance.

Background: The increasing volume and complexity of high-throughput genomic data make analysis and prioritization of variants difficult for researchers with limited bioinformatics skills. Variant Ranker allows researchers to rank identified variants and determine the most confident variants for experimental validation.

Results: We describe Variant Ranker, a user-friendly simple web-based tool for ranking, filtering and annotation of coding and non-coding variants.

Activation of NLRP3 Inflammasome in Inflammatory Bowel Disease: Differences Between Crohn's Disease and Ulcerative Colitis.

Background: NLRP3 inflammasome is a multimolecular cytosol complex that, when activated, contributes to the cleavage of pro-interleukin (IL)-1β to IL-1β.

Aims: To investigate NLRP3 inflammasome activation in inflammatory bowel disease.

Methods: Peripheral blood mononuclear cells from Crohn's disease (CD), ulcerative colitis (UC) patients and controls were stimulated with LPS in the absence or presence of MSU.

Defective production of interleukin-1 beta in patients with type 2 diabetes mellitus: Restoration by proper glycemic control.

The underlying immune defect of susceptibility in diabetes mellitus type 2 to infections remains unknown. The qualitative changes in cytokine biosynthesis by circulating mononuclear cells (PBMCs) and its modulation by glycemic control were investigated. PBMCs were isolated from 39 patients and 25 controls.

Targeted Re-Sequencing Approach of Candidate Genes Implicates Rare Potentially Functional Variants in Tourette Syndrome Etiology.

Although the genetic basis of Tourette Syndrome (TS) remains unclear, several candidate genes have been implicated. Using a set of 382 TS individuals of European ancestry we investigated four candidate genes for TS (, and ) in an effort to identify possibly causal variants using a targeted re-sequencing approach by next generation sequencing technology. Identification of possible disease causing variants under different modes of inheritance was performed using the algorithms implemented in VAAST.

The Genetic Etiology of Tourette Syndrome: Large-Scale Collaborative Efforts on the Precipice of Discovery.

Gilles de la Tourette Syndrome (TS) is a childhood-onset neurodevelopmental disorder that is characterized by multiple motor and phonic tics. It has a complex etiology with multiple genes likely interacting with environmental factors to lead to the onset of symptoms. The genetic basis of the disorder remains elusive.

Meta-Analysis of Tourette Syndrome and Attention Deficit Hyperactivity Disorder Provides Support for a Shared Genetic Basis.

Gilles de la Tourette Sydrome (TS) is a childhood onset neurodevelopmental disorder, characterized phenotypically by the presence of multiple motor and vocal tics. It is often accompanied by multiple psychiatric comorbidities, with Attention Deficit/Hyperactivity Disorder (ADHD) among the most common. The extensive co-occurrence of the two disorders suggests a shared genetic background.

Predictive value of biochemical marker ADAM-12 at first trimester of pregnancy for hypertension and intrauterine growth restriction.

Purpose: Delineate whereas ADAM-12 levels at first trimester of pregnancy may be used as a marker for hypertension-preeclampsia (PE) and intrauterine growth restriction (IUGR).

Materials And Methods: The present is a case control study. Serum ADAM-12 of women presenting for routine assessment of risk for chromosomal abnormalities at 11+0 to 13+6 weeks of gestation was measured.

Individualized significance of the -251 A/T single nucleotide polymorphism of interleukin-8 in severe infections.

Based on the concept of the individualized nature of sepsis, we investigated the significance of the -251 A/T (rs4073) single nucleotide polymorphism (SNP) of interleukin (IL)-8 in relation to the underlying infection. Genotyping was performed in 479 patients with severe acute pyelonephritis (UTI, n = 146), community-acquired pneumonia (CAP, n = 109), intra-abdominal infections (IAI, n = 119), and primary bacteremia (BSI, n = 105) by restriction fragment length polymorphism of the polymerase chain reaction (PCR) product and compared with 104 healthy volunteers. Circulating IL-8 was measured within the first 24 h of diagnosis by an immunosorbent assay.

Interactions of Klebsiella pneumoniae with the innate immune system vary in relation to clone and resistance phenotype.

Apart from inadequate antimicrobial treatment, specific virulence factors contribute to the high attributable mortality of infections caused by multidrug-resistant (MDR) Klebsiella pneumoniae. We explored the roles of MDR and clones as virulence determinants of K. pneumoniae and their interaction with innate immunity.

NK and NKT Cell Depletion Alters the Outcome of Experimental Pneumococcal Pneumonia: Relationship with Regulation of Interferon-γ Production.

Background. Natural killer (NK) and natural killer T (NKT) cells contribute to the innate host defense but their role in bacterial sepsis remains controversial. Methods.