Publications by authors named "B-M Kleber"
Article Synopsis
- * Discovery of 7 new genetic loci associated with FVIII and 1 new locus for VWF, supporting their roles in thrombotic outcomes via Mendelian randomization.
- * Functional testing revealed that silencing genes like B3GNT2 and CD36 impacted FVIII and VWF release from endothelial cells, indicating their potential regulatory roles.
Article Synopsis
- X-chromosomal genetic variants can provide important information about differences in human traits and diseases between sexes.
- A large-scale study analyzed kidney-related traits in nearly 909,000 individuals, finding 23 genetic loci linked to uric acid levels and estimated glomerular filtration rate (eGFR), including four new genes that may play a role in kidney function.
- The research also discovered five novel sex-specific interactions, with variations showing different effects in males and females, and highlighted genes that are responsive to androgens (male hormones), indicating a complex relationship between sex and kidney-related genetics.
Article Synopsis
- This study examines the relationship between resting heart rate and cardiovascular diseases, identifying 493 genetic variants linked to this trait through a large-scale analysis of 835,465 individuals.
- It highlights the significance of higher genetically predicted resting heart rates, which are associated with an increased risk of dilated cardiomyopathy but lower risk for conditions like atrial fibrillation and ischemic strokes.
- The study also challenges previous findings on resting heart rate and all-cause mortality, suggesting earlier results may have been influenced by biases, ultimately enhancing our understanding of the biological implications of resting heart rate in cardiovascular health.
Insulin secretion is critical for glucose homeostasis, and increased levels of the precursor proinsulin relative to insulin indicate pancreatic islet beta-cell stress and insufficient insulin secretory capacity in the setting of insulin resistance. We conducted meta-analyses of genome-wide association results for fasting proinsulin from 16 European-ancestry studies in 45,861 individuals. We found 36 independent signals at 30 loci (p value < 5 × 10), which validated 12 previously reported loci for proinsulin and ten additional loci previously identified for another glycemic trait.
View Article and Find Full Text PDFArticle Synopsis
- Researchers studied the genetic connections to blood fats using data from 1.6 million people from different backgrounds to understand why certain fats are higher or lower in the body.
- They looked at special genes and how they interact in the liver and fat cells, finding that the liver plays a big part in controlling fat levels.
- Two specific genes, CREBRF and RRBP1, were highlighted as important in understanding how our bodies manage fats due to strong supporting evidence.
Article Synopsis
- Scientists studied people's genetics to learn about traits related to blood sugar, which helps diagnose and monitor type 2 diabetes.
- Most of the earlier studies only looked at people with European backgrounds, but this research included many more individuals from different backgrounds, finding 242 important genetic spots linked to blood sugar levels.
- By studying a diverse group of people, they discovered new insights about how diabetes works in the body, helping to uncover different biological processes for each glycemic trait.
Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls.
View Article and Find Full Text PDFIn many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F) for >1.
View Article and Find Full Text PDFChronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178).
View Article and Find Full Text PDFArticle Synopsis
- The study investigated the genetic variant rs1333049 at chromosome 9p21 to see its impact on subsequent coronary heart disease (CHD) events in over 100,000 Europeans with existing CHD.
- Results indicated no significant association between the variant and the risk of CHD death or myocardial infarction among those already diagnosed, contrasting with a strong link found in a separate group of CHD cases compared to healthy controls.
- There was a slight positive correlation found between the variant and subsequent revascularization procedures, suggesting some potential role in this specific outcome, but overall, the variant did not predict acute CHD events for those already affected.
Background: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD.
Methods: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events.
Factor VII (FVII) is an important component of the coagulation cascade. Few genetic loci regulating FVII activity and/or levels have been discovered to date. We conducted a meta-analysis of 9 genome-wide association studies of plasma FVII levels (7 FVII activity and 2 FVII antigen) among 27 495 participants of European and African ancestry.
View Article and Find Full Text PDFArticle Synopsis
- - The study investigates the genetic factors influencing plasma levels of Factor VIII (FVIII) and von Willebrand factor (VWF), which are linked to both clotting disorders and thrombosis risk, using data from over 46,000 individuals across various ethnic backgrounds.
- - Researchers discovered 13 new genetic associations with FVIII and VWF levels, including 7 associated with FVIII and 11 with VWF, extending the knowledge beyond previously known variants. Functional tests supported most of these associations.
- - The analysis suggests that higher plasma levels of FVIII may contribute to increased risk of venous thrombosis and coronary artery disease, while elevated VWF levels might heighten the risk of ischemic stroke, highlighting the potential for these proteins
Article Synopsis
- Many genome-wide association studies (GWAS) often overlook environmental factors like smoking, which might affect the genetic analysis of obesity traits.
- This study analyzed GWAS data from over 240,000 participants, including smokers and nonsmokers, to find genetic links to body mass index (BMI) and body fat distribution.
- The researchers identified 23 new genetic loci related to obesity and 9 loci that interact with smoking, suggesting that smoking can influence genetic predispositions to body fat.
Background: Analysis of myocardium has revealed mechanistic insights into arrhythmogenic cardiomyopathy but cardiac samples are difficult to obtain from probands and especially from family members. To identify a potential surrogate tissue, we characterized buccal mucosa cells.
Methods And Results: Buccal cells from patients, mutation carriers, and controls were immunostained and analyzed in a blinded fashion.
Article Synopsis
- Researchers analyzed data from 14 studies involving nearly 27,000 participants to find genetic factors influencing the levels of tissue plasminogen activator (tPA), a key enzyme in blood clot breakdown.
- They identified three significant genetic loci associated with tPA levels: one linked to the STXBP5 gene on chromosome 6, another near the PLAT gene on chromosome 8, and a third related to the STX2 gene on chromosome 12.
- Functional tests showed that silencing STXBP5 reduces tPA release from cells, while silencing STX2 increases it, suggesting these genes play important roles in regulating tPA levels.