Publications by authors named "Schormair B"

Aims: The Cardiac Conduction System (CCS) is progressively specified during development by interactions among a discrete number of Transcriptions Factors that ensure its proper patterning and the emergence of its functional properties. Meis genes encode homeodomain transcription factors (TFs) with multiple roles in mammalian development. In humans, Meis genes associate with congenital cardiac malformations and alterations of cardiac electrical activity, however the basis for these alterations has not been established.

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  • MEIS1 and MEIS2 are important genes that code for proteins involved in development across various tissues, particularly in the brain, but their specific roles in early neural differentiation need further investigation.
  • Research involving knockout and overexpression of these genes in human neural stem cells reveals that MEIS1 and MEIS2 regulate different groups of target genes linked to various biological functions.
  • MEIS1 is not only connected to gene regulation, especially in relation to other transcription factors, but it also has a significant risk factor for restless legs syndrome (RLS), as it controls genes associated with this condition.
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  • A large-scale genome-wide association study (GWAS) was conducted with over 6000 participants to investigate genetic risk factors for isolated dystonia, aiming to improve upon earlier studies that found no significant genetic links.
  • The study included 4303 dystonia patients and 2362 healthy controls, analyzing various factors like age of onset and affected body areas, but ultimately failed to identify any common genetic variants associated with dystonia.
  • The findings suggest that isolated dystonia may not be influenced by common genetic variations, highlighting the need for more extensive studies like whole-genome sequencing to uncover potential genetic contributions.
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  • Restless legs syndrome (RLS) affects nearly 10% of older adults, but many face delays in diagnosis and treatment.
  • A large-scale genetic study identified 164 risk loci for RLS, enhancing our understanding of its genetic basis and showing similarities in genetic predispositions between sexes.
  • Findings suggest potential drug targets, a relationship between RLS and diabetes, and highlight the effectiveness of machine learning in predicting RLS risk using genetic and other data.
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Background: The dicarbonyl compounds methylglyoxal (MG), glyoxal (GO) and 3-deoxyglucosone (3-DG) have been linked to various diseases. However, disease-independent phenotypic and genotypic association studies with phenome-wide and genome-wide reach, respectively, have not been provided.

Methods: MG, GO and 3-DG were measured by LC-MS in 1304 serum samples of two populations (KORA, n = 482; BiDirect, n = 822) and assessed for associations with genome-wide SNPs (GWAS) and with phenome-wide traits.

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  • The study investigates the role of DNA methylation in the pathophysiology of idiopathic restless legs syndrome (RLS), aiming to develop a potential biomarker based on blood DNA analysis.
  • Utilizing a large sample size across multiple cohorts, researchers identified numerous significant CpG sites linked to specific genes in both blood and brain tissues, with gene-set analysis revealing connections to neurodevelopmental traits.
  • The proposed epigenetic risk score shows promise with a validation area under the curve (AUC) of 0.70, but further refinement is needed for it to be reliable as a biomarker for RLS.
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  • * Student attitudes shifted towards a more critical view of personal genotyping, with a significant majority agreeing that genetic analyses should involve genetic counseling.
  • * Overall, students found the personal genotyping aspect to be useful and strongly recommended its inclusion in future genomics courses.
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Restless legs syndrome (RLS) is a common sleep-related movement disorder in populations of European descent and disease risk is strongly influenced by genetic factors. Common variants have been assessed extensively in several genome-wide association studies, but the contribution of rarer genetic variation has not been investigated at this scale. We therefore genotyped a case-control set of 9246 individuals for mainly rare and low frequency exonic variants using the Illumina ExomeChip.

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Study Objectives: Several candidate gene studies have been published for idiopathic restless legs syndrome (RLS) in populations of European ancestry, but the reported associations have not been confirmed in independent samples. Our aim was to reassess these findings in a large case-control dataset in order to evaluate their validity.

Methods: We screened PubMed for RLS candidate gene studies.

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Restless legs syndrome (RLS) is a common sensorimotor disorder characterized by an urge to move that appears during rest or is exacerbated by rest, that occurs in the evening or night and that disappears during movement or is improved by movement. Symptoms vary considerably in age at onset, frequency and severity, with severe forms affecting sleep, quality of life and mood. Patients with RLS often display periodic leg movements during sleep or resting wakefulness.

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  • Dystonia is a common movement disorder causing involuntary abnormal postures, and researchers have identified a specific biomarker for KMT2B-deficient dystonia, a notable subtype of this disorder.
  • The biomarker was developed using a support vector machine to analyze 113 DNA CpG sites in blood cells, revealing significant changes in methylation linked to KMT2B deficiency.
  • This finding not only helps classify patients accurately but also correlates their methylation levels with the age of onset of dystonia, offering insights for potential treatments like deep brain stimulation and monitoring disease progression.
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Recent developments in the genetics of restless legs syndrome (RLS) revealed associations of disease risk with genetic loci containing the genes coding cereblon, the protein bound by thalidomide, and its endogenous substrate MEIS2, whose degradation is inhibited by the thalidomide-cereblon interaction. Therefore it was hypothesized that thalidomide may be a potential treatment option for RLS. Here we report on the therapeutic effect of thalidomide in a patient with otherwise treatment-resistant RLS who received 100 mg thalidomide off-label for 3 weeks.

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Objective: Impaired lysosomal degradation of α-synuclein and other cellular constituents may play an important role in Parkinson's disease (PD). Rare genetic variants in the glucocerebrosidase (GBA) gene were consistently associated with PD. Here we examine the association between rare variants in lysosomal candidate genes and PD.

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  • Restless legs syndrome (RLS) is a common neurological disorder affecting individual well-being and public health, with identified genetic risk loci but unclear causative genes.
  • A study analyzed 84 candidate genes in nearly 9,600 participants using advanced sequencing methods, finding significant low-frequency and rare variant burdens associated with RLS.
  • Fourteen genes were identified as potentially causative, with nine located near known RLS loci, while five were newly associated with the disorder, highlighting new avenues for further research and understanding.
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Insomnia is a common disorder linked with adverse long-term medical and psychiatric outcomes. The underlying pathophysiological processes and causal relationships of insomnia with disease are poorly understood. Here we identified 57 loci for self-reported insomnia symptoms in the UK Biobank (n = 453,379) and confirmed their effects on self-reported insomnia symptoms in the HUNT Study (n = 14,923 cases and 47,610 controls), physician-diagnosed insomnia in the Partners Biobank (n = 2,217 cases and 14,240 controls), and accelerometer-derived measures of sleep efficiency and sleep duration in the UK Biobank (n = 83,726).

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After an impressively successful application as a research instrument, whole-exome sequencing (WES) now enters the clinical practice due to its high diagnostic, time, and economic efficiency. WES is the diagnostic method of choice for symptoms that may be due to many different monogenic causes. Neurological indications include movement disorders, especially in cases of early symptom onset, familial clustering and complex manifestation.

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Restless legs syndrome, also known as Willis-Ekbom disease, is a common neurological condition whose manifestation is affected by complex environmental and genetic interactions. Restless legs syndrome can occur on its own, mostly at a young age, or with comorbidities such as cardiovascular disease, diabetes, and arterial hypertension, making it a difficult condition to properly diagnose. However, the concept of restless legs syndrome as being two entities, primary or secondary to another condition, has been challenged with genetic data providing further insight into the pathophysiology of the condition.

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Background: Restless legs syndrome is a prevalent chronic neurological disorder with potentially severe mental and physical health consequences. Clearer understanding of the underlying pathophysiology is needed to improve treatment options. We did a meta-analysis of genome-wide association studies (GWASs) to identify potential molecular targets.

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Parkinson's disease (PD) is a genetically heterogeneous disorder and new putative disease genes are discovered constantly. Therefore, whole-exome sequencing could be an efficient approach to genetic testing in PD. To evaluate its performance in early-onset sporadic PD, we performed diagnostic exome sequencing in 80 individuals with manifestation of PD symptoms at age 40 or earlier and a negative family history of PD.

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Meis homeobox 1 (Meis1) is a transcription factor functioning in the development of the nervous system and the cardiovascular system. Both common and rare variants within the gene have been associated with restless legs syndrome (RLS), while its association with symptoms of insomnia has also been discovered recently. RLS is associated with sleep disturbances, and while Meis1 haploinsufficiency is one of the most promising strategies for an RLS animal model, sleep phenotyping of Meis1 knockout mice has never been conducted.

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encodes a developmental transcription factor and has been linked to restless legs syndrome (RLS) in genome-wide association studies. RLS is a movement disorder leading to severe sleep reduction and has a substantial impact on the quality of life of patients. In genome-wide association studies, has consistently been the gene with the highest effect size and functional studies suggest a disease-relevant downregulation.

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Persistent insomnia is among the most frequent complaints in general practice. To identify genetic factors for insomnia complaints, we performed a genome-wide association study (GWAS) and a genome-wide gene-based association study (GWGAS) in 113,006 individuals. We identify three loci and seven genes associated with insomnia complaints, with the associations for one locus and five genes supported by joint analysis with an independent sample (n = 7,565).

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At the outset of genetic studies in restless legs syndrome (RLS), the disorder was assumed to be a classical monogenic disorder that runs in families. However, years of family studies did not reveal any causally-related genes or genetic variants. The advent of high-throughput genotyping technology led to a change; genome-wide association studies in large case-control samples became feasible, which led to the identification of first genetic risk variants for RLS.

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Background: Dystonia is clinically and genetically heterogeneous. Despite being a first-line testing tool for heterogeneous inherited disorders, whole-exome sequencing has not yet been evaluated in dystonia diagnostics. We set up a pilot study to address the yield of whole-exome sequencing for early-onset generalized dystonia, a disease subtype enriched for monogenic causation.

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