Publications by authors named "Lange L"
Recent advancements in Parkinson's disease (PD) drug development have been significantly driven by genetic research. Importantly, drugs supported by genetic evidence are more likely to be approved. While genome-wide association studies (GWAS) are a powerful tool to nominate genomic regions associated with certain traits or diseases, pinpointing the causal biologically relevant gene is often challenging.
View Article and Find Full Text PDFAims/hypothesis: This is the first study to examine the association between variants of the glucagon-like-peptide-1 receptor gene (GLP-1R) and metabolic characteristics among youth. We explored separate associations of three GLP-1R polymorphisms (rs10305420, rs6923761, and rs1042044) with BMI trajectories and markers of glucose-insulin homeostasis.
Methods: Mixed models examined associations between GLP-1R polymorphisms and trajectories of BMI.
The pulp of açaí palm fruits ( Mart.) is a valuable export commodity in Brazil. Its production generates 1.
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- Frontal alpha asymmetry was thought to indicate levels of approach motivation, but recent studies found little connection between it and personality traits.
- A study using data from the CoScience project (n=740) measured frontal asymmetry during different tasks to see if it varied based on approach motivation.
- The results showed that frontal asymmetry wasn't significantly influenced by the tasks and did not correlate with self-reported personality traits, undermining its validity as a marker for approach motivation.
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- The release of Genome Aggregation Database (gnomAD) v4 significantly increases sample size, impacting the interpretation of genetic variants, particularly in dystonia.
- A comparison of variants linked to common forms of isolated dystonia showed that most (77.7%) remained absent in the new version; however, some well-known pathogenic variants were newly recorded in v4.
- Despite finding more dystonia-related alleles in gnomAD v4, the authors stress that the presence of these variants in population data doesn't automatically mean they aren't pathogenic.
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- Researchers studied plasma proteomic profiles linked to subclinical mutations in blood cells, particularly focusing on clonal hematopoiesis of indeterminate potential (CHIP) and its connection to various health outcomes, including coronary artery disease (CAD).
- The study involved a large, diverse group of participants and identified a significant number of unique proteins associated with key driver genes, showing differences based on genetics, sex, and race.
- Methods like Mendelian randomization and mouse model tests helped clarify the causal effects of these proteins, revealing shared plasma proteins between CHIP and CAD that could inform future clinical insights.
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- A study explored how different biological factors (like proteins and metabolites) can help identify distinct groups of people with obesity who have varying risks for heart and metabolic diseases.
- Using data from 243 participants, researchers found two groups: one (iCluster1) with favorable cholesterol levels and another (iCluster2) with higher BMI and inflammation levels.
- The findings suggest these groups could reflect different stages of obesity-related issues, potentially influenced by factors like diet and behavior, despite similar ages across the groups.
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- Knowledge of the genetic factors contributing to Parkinson's disease has significantly expanded, starting from the identification of the first mutation in α-synuclein to discovering various other related genes.
- Genetic research helps understand the diverse symptoms of Parkinson's disease and promotes the search for new biomarkers and treatment options, with several clinical trials in progress.
- Efforts to include previously under-represented populations in genetic studies are fostering collaboration and promising new insights, although challenges persist, offering opportunities for a more comprehensive understanding of the disease worldwide.
Importance: The clinical utility of polygenic risk scores (PRS) for blood pressure (BP) response to antihypertensive treatment (AHT) has not been elucidated.
Objective: To investigate the ability of a systolic BP (SBP) PRS to predict AHT response and apparent treatment-resistant hypertension (aTRH).
Design, Setting, And Participants: The Genetics of Hypertension Associated Treatments (GenHAT) study was an ancillary pharmacogenomic study to the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).
The Parkinson's Families Project is a UK-wide study aimed at identifying genetic variation associated with familial and early-onset Parkinson's disease (PD). We recruited individuals with a clinical diagnosis of PD and age at motor symptom onset ≤45 years and/or a family history of PD in up to third-degree relatives. Where possible, we also recruited affected and unaffected relatives.
View Article and Find Full Text PDFDespite the biomedical importance of haematopoietic stem cells and haematopoietic progenitor cells, their in vitro stabilization in a developmental context has not been achieved due to limited knowledge of signals and markers specifying the multiple haematopoietic waves as well as ethically restricted access to the human embryo. Thus, an in vitro approach resembling aspects of haematopoietic development in the context of neighbouring tissues is of interest. Our established human pluripotent stem cell-derived heart-forming organoids (HFOs) recapitulate aspects of heart, vasculature and foregut co-development.
View Article and Find Full Text PDFPathogenic variants in the gene represent the most common cause of autosomal dominant Parkinson's disease (PD) worldwide. We identified the p.L1795F variant in 14 White/European ancestry PD patients, including two families with multiple affected carriers and seven additional affected individuals with familial PD using genotyping and sequencing data from more than 50,000 individuals through GP2, AMP-PD, PDGENEration, and CENTOGENE.
View Article and Find Full Text PDFAims/hypothesis: Several studies have reported associations between specific proteins and type 2 diabetes risk in European populations. To better understand the role played by proteins in type 2 diabetes aetiology across diverse populations, we conducted a large proteome-wide association study using genetic instruments across four racial and ethnic groups: African; Asian; Hispanic/Latino; and European.
Methods: Genome and plasma proteome data from the Multi-Ethnic Study of Atherosclerosis (MESA) study involving 182 African, 69 Asian, 284 Hispanic/Latino and 409 European individuals residing in the USA were used to establish protein prediction models by using potentially associated cis- and trans-SNPs.
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- Genome-wide association studies have found numerous genetic loci linked to glycemic traits, but connecting these loci to specific genes and biological pathways remains a challenge.
- Researchers conducted meta-analyses of exome-array studies across four glycemic traits, analyzing data from over 144,000 participants, which led to the identification of coding variant associations in more than 60 genes.
- The study revealed significant pathways related to insulin secretion, zinc transport, and fatty acid metabolism, enhancing understanding of glycemic regulation and making data available for further research.
In recent years, microbiomes and their potential applications for human, animal or plant health, food production and environmental management came into the spotlight of major national and international policies and strategies. This has been accompanied by substantial R&D investments in both public and private sectors, with an increasing number of products entering the market. Despite widespread agreement on the potential of microbiomes and their uses across disciplines, stakeholders and countries, there is no consensus on what defines a microbiome application.
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- Genetic studies have highlighted the need for more diverse research on plasma fibrinogen levels, as previous studies largely focused on Europeans, leading to gaps in understanding and missing heritability.
- By analyzing data from whole-genome sequencing and genotype data from large cohorts, researchers identified 18 genetic loci related to fibrinogen levels, some of which are more common in African populations and include variants that may impact protein function.
- The study's findings indicate a connection between fibrinogen levels and various health conditions, emphasizing the importance of whole-genome sequencing in discovering genetic factors in diverse populations and enhancing knowledge about fibrinogen regulation.
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- Researchers investigated blood protein networks in chronic obstructive pulmonary disease (COPD) using data from over 3,000 participants to better understand complex interconnections rather than just individual biomarker changes.
- They applied advanced techniques to analyze 4,776 proteins, identifying significant networks linked to factors like smoking status and emphysema.
- The study found both known and new proteins associated with COPD, highlighting the importance of these networks in understanding the disease across different ethnic groups, with some results replicating in another study cohort.
Background: Hymenoptera venom is one of the most frequent causes of anaphylaxis. Studies from adults indicate the clinical profiles and risk factors of Hymenoptera venom-induced anaphylaxis (VIA). Much less is known about pediatric VIA.
View Article and Find Full Text PDFBackground: Here we describe our experience managing intracranial dural arteriovenous fistulas (DAVFs) via endovascular embolization using a transarterial embolization (TAE) technique with liquid embolic agents. We illustrate the technical nuance of using dual arterial access for angiographic control runs in complex DAVFs supplied by multiple feeders from 2 distinct arterial systems.
Methods: Retrospective analysis of intracranial DAVF embolization as a single treatment technique at our institution from 2013 to 2023.
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- Current estimates of genetic variants linked to Parkinson's disease (PD) show limitations and biases across different populations, complicating patient recruitment for clinical trials focused on genetic therapies.
- The Rostock Parkinson's disease (ROPAD) study analyzes data from 12,580 PD patients across 16 countries, revealing that 14.8% had a genetic test positive for PD-related variants, particularly in specific genes like GBA1 and LRRK2.
- Findings indicate higher positivity rates in patients with earlier onset (age ≤ 50) or a positive family history, emphasizing the need for more extensive genetic investigation to improve patient stratification for future clinical trials.
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- Chronic kidney disease (CKD) affects about 1 in 7 adults in the U.S., especially African Americans who are more likely to suffer from it.
- Scientists discovered that certain changes in DNA can help predict who might get CKD, focusing on specific sites in the DNA.
- The study created a special score using these DNA changes to see how likely someone is to have CKD and found it works well for African Americans, suggesting it could help in checking kidney health in the future.
Background: Until recently, about three-quarters of all monogenic Parkinson's disease (PD) studies were performed in European/White ancestry, thereby severely limiting our insights into genotype-phenotype relationships at a global scale.
Objective: To identify the multi-ancestry spectrum of monogenic PD.
Methods: The first systematic approach to embrace monogenic PD worldwide, The Michael J.
Prior research suggests that cognitive control, indicated by NoGo N2 amplitudes in Go/NoGo tasks, is associated with dispositional anxiety. This negative association tends to be reduced in anxiety-enhancing experimental conditions. However, anxiety-reducing conditions have not yet been investigated systematically.
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