Publications by authors named "Hans M Munter"
Article Synopsis
- Cerebral small vessel disease (cSVD) is a major contributor to stroke and dementia, and currently lacks specific treatments, prompting a study using Mendelian randomization to identify protein associations.
- The research combined cerebrospinal fluid (CSF) and plasma data with genetic studies to identify 49 proteins linked to cSVD, highlighting 16 that appeared in both fluids and showing connections to immune response and extracellular matrix pathways.
- Notably, many identified proteins were associated with stroke and dementia, with some already having known drug targets, paving the way for potential new biomarkers and therapies for cSVD.
Characteristic cerebral pathological changes of Alzheimer's disease (AD) such as glucose hypometabolism or the accumulation of cleavage products of the amyloid precursor protein (APP), known as Aβ peptides, lead to sustained endoplasmic reticulum (ER) stress and neurodegeneration. To preserve ER homeostasis, cells activate their unfolded protein response (UPR). The rhomboid-like-protease 4 (RHBDL4) is an enzyme that participates in the UPR by targeting proteins for proteasomal degradation.
View Article and Find Full Text PDFLarge-scale imputation reference panels are currently available and have contributed to efficient genome-wide association studies through genotype imputation. However, whether large-size multi-ancestry or small-size population-specific reference panels are the optimal choices for under-represented populations continues to be debated. We imputed genotypes of East Asian (180k Japanese) subjects using the Trans-Omics for Precision Medicine reference panel and found that the standard imputation quality metric (Rsq) overestimated dosage r2 (squared correlation between imputed dosage and true genotype) particularly in marginal-quality bins.
View Article and Find Full Text PDFPeptic ulcer disease (PUD) refers to acid-induced injury of the digestive tract, occurring mainly in the stomach (gastric ulcer (GU)) or duodenum (duodenal ulcer (DU)). In the present study, we conducted a large-scale, cross-ancestry meta-analysis of PUD combining genome-wide association studies with Japanese and European studies (52,032 cases and 905,344 controls), and discovered 25 new loci highly concordant across ancestries. An examination of GU and DU genetic architecture demonstrated that GUs shared the same risk loci as DUs, although with smaller genetic effect sizes and higher polygenicity than DUs, indicating higher heterogeneity of GUs.
View Article and Find Full Text PDFArticle Synopsis
- The study aims to uncover new genetic factors linked to calcific aortic stenosis (AS) and identify mechanisms through functional and expression data integration.
- A large genome-wide meta-analysis involving over 653,000 European participants found 17 significant genetic loci associated with AS, with further support for their involvement from independent cohorts.
- Findings highlight the roles of dyslipidemia, inflammation, calcification, and obesity in AS development, suggesting potential new strategies for treatment and prevention.
Article Synopsis
- * A study screened nearly 5,000 plasma proteins and identified 1,216 influenced by body mass index, discovering nephronectin (NPNT) as a key protein linked to worse COVID-19 outcomes.
- * NPNT was found to be expressed in lung cells of those who died from COVID-19 and was linked to increased illness severity, suggesting that managing body fat could lower NPNT levels and potentially improve COVID-19 outcomes.
Rationale: Dextro-transposition of the great arteries (D-TGA) is a severe congenital heart defect which affects approximately 1 in 4,000 live births. While there are several reports of D-TGA patients with rare variants in individual genes, the majority of D-TGA cases remain genetically elusive. Familial recurrence patterns and the observation that most cases with D-TGA are sporadic suggest a polygenic inheritance for the disorder, yet this remains unexplored.
View Article and Find Full Text PDFArticle Synopsis
- Poor sleep quality can negatively affect health, and while sleep has genetic components, the specific genes involved are not well understood.
- Researchers conducted a genome-wide association study (GWAS) with the Pittsburgh Sleep Quality Index (PSQI), identifying two new genetic markers on chromosomes 2 and 7 linked to sleep quality.
- Further analysis and experiments confirmed the role of the NPY gene and revealed a new sleep-related gene, MPP6, which affects sleep duration in model organisms.
Article Synopsis
- Aortic stenosis (AS) currently has no approved medical treatment, prompting researchers to explore genetic factors and pathways associated with the condition to identify potential drug targets.
- A genome-wide association study analyzed data from 44,703 participants, including 3,469 diagnosed with AS, along with additional replication cohorts, revealing significant genetic associations and links to fatty acid levels in the blood.
- The study identified a notable genetic variant (rs174547) that was correlated with a reduced likelihood of developing AS and found connections between blood fatty acid ratios and aortic valve calcium presence, highlighting potential areas for future research and treatment strategies.*
Parasitic helminths cause significant damage as they migrate through host tissues to complete their life cycle. While chronic helminth infections are characterized by a well-described Type 2 immune response, the early, tissue-invasive stages are not well understood. Here we investigate the immune pathways activated during the early stages of Heligmosomoides polygyrus bakeri (Hpb), a natural parasitic roundworm of mice.
View Article and Find Full Text PDFArticle Synopsis
- Researchers conducted whole-exome and whole-genome sequencing on nearly 3,000 Alzheimer’s disease cases and controls from France to investigate genetic associations.
- They found significant links between early-onset Alzheimer’s (EOAD) risk and rare variants in three specific genes: SORL1, TREM2, and ABCA7, but not in late-onset Alzheimer’s (LOAD).
- The study reaffirmed previous findings on these genes and highlighted that variations in TREM2, SORL1, and ABCA7 each explain a small portion (1.1% to 1.5%) of EOAD heritability, much less than the substantial impact of the APOE ε4 variant (9.12
Objective: To study the association between ABCA7 rare coding variants and Alzheimer disease (AD) in a case-control setting.
Methods: We conducted a whole exome analysis among 484 French patients with early-onset AD and 590 ethnically matched controls.
Results: After collapsing rare variants (minor allele frequency ≤1%), we detected an enrichment of ABCA7 loss of function (LOF) and predicted damaging missense variants in cases (odds ratio [OR] 3.
Causative variants in APP, PSEN1 or PSEN2 account for a majority of cases of autosomal dominant early-onset Alzheimer disease (ADEOAD, onset before 65 years). Variant detection rates in other EOAD patients, that is, with family history of late-onset AD (LOAD) (and no incidence of EOAD) and sporadic cases might be much lower. We analyzed the genomes from 264 patients using whole-exome sequencing (WES) with high depth of coverage: 90 EOAD patients with family history of LOAD and no incidence of EOAD in the family and 174 patients with sporadic AD starting between 51 and 65 years.
View Article and Find Full Text PDF