Publications by authors named "Theriault S"

Background: Lp(a) (lipoprotein(a)) is an independent risk factor for calcific aortic valve stenosis (CAVS). Whether patients with CAVS and high Lp(a) levels are at higher risk of valvular or cardiovascular events is unknown. The aim of this study is to determine whether higher Lp(a) levels are associated with valvular and cardiovascular outcomes in patients with CAVS.

View Article and Find Full Text PDF

Background: Therapies targeting the LPL (lipoprotein lipase) pathway are under development for cardiometabolic disease. Insights into their efficacy-both alone and in combination with existing lipid-lowering therapies-modes of action, and safety of these agents are essential to inform clinical development. Using Mendelian randomization, we aimed to (1) evaluate efficacy, (2) explore shared mechanisms, (3) assess additive effects with approved lipid-lowering drugs, and (4) identify secondary indications and potential adverse effects.

View Article and Find Full Text PDF

Atrial fibrillation (AF) is the most common heart rhythm abnormality and is a leading cause of heart failure and stroke. This large-scale meta-analysis of genome-wide association studies increased the power to detect single-nucleotide variant associations and found more than 350 AF-associated genetic loci. We identified candidate genes related to muscle contractility, cardiac muscle development and cell-cell communication at 139 loci.

View Article and Find Full Text PDF

Background Gene-environment interactions may enhance our understanding of hypertension. Our previous study highlighted the importance of considering psychosocial factors in gene discovery for blood pressure (BP) but was limited in statistical power and population diversity. To address these challenges, we conducted a multi-population genome-wide association study (GWAS) of BP accounting for gene-depressive symptomatology (DEPR) interactions in a larger and more diverse sample.

View Article and Find Full Text PDF

Background And Aims: Estimating the genetic risk of coronary artery disease (CAD) is now possible by aggregating data from genome-wide association studies (GWAS) into polygenic risk scores (PRS). Combining multiple PRS for specific circulating blood lipids could improve risk prediction. Here, we sought to evaluate the performance of PRS derived from CAD and blood lipids GWAS to predict the incidence of CAD.

View Article and Find Full Text PDF
Article Synopsis
  • Acute pancreatitis (AP) is often triggered by gallstones, alcohol, or high triglycerides, and this study explores the genetic factors that could help identify individuals at higher risk for AP.
  • Researchers analyzed genetic data from nearly 485,000 individuals to create a weighted polygenic risk score (PRS) using specific genetic variants linked to pancreatitis.
  • Those with a higher pancreatitis PRS (above the 90th percentile) had a significantly increased risk of developing AP, suggesting that this genetic information can aid in identifying patients who might need closer monitoring and intervention.
View Article and Find Full Text PDF

Although both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discover 22 novel gene-sleep duration interaction loci for blood pressure, mapped to 23 genes.

View Article and Find Full Text PDF
Article Synopsis
  • There are currently no drugs available to slow the progression of aortic stenosis, and while plasma lipoprotein(a) levels may predict its onset, their role in disease progression is debated.
  • A study involving 710 patients from Canada and the UK examined the relationship between plasma lipoprotein(a) concentrations and hemodynamic changes in aortic stenosis.
  • Results showed that patients with higher lipoprotein(a) levels experienced significantly faster progression in peak aortic jet velocity and mean transvalvular gradient, suggesting that elevated lipoprotein(a) may contribute to worse outcomes in aortic stenosis patients.
View Article and Find Full Text PDF

Background: The most near-term clinical application of genome-wide association studies in lung cancer is a polygenic risk score (PRS).

Methods: A case-control dataset was generated consisting of 4002 lung cancer cases from the LORD project and 20,010 ethnically matched controls from CARTaGENE. A genome-wide PRS including >1.

View Article and Find Full Text PDF
Article Synopsis
  • Anticoagulants are commonly used to prevent blood clots, but there are significant risks, especially bleeding, with long-term use, highlighting the need for safer alternatives.
  • Researchers used genetic analysis methods on large data sets to investigate 26 proteins associated with the coagulation process, finding specific proteins (F2 and F11) that may provide effective prevention of blood clots with lower bleeding risks.
  • The study suggests that reducing levels of the proteins F2 and F11 could help improve patient safety and efficacy for those requiring anticoagulation therapy.
View Article and Find Full Text PDF

Cardiac troponin is extensively used as a biomarker in modern medicine due to its diagnostic capability for myocardial injury, as well as its predictive and prognostic value for cardiac diseases. However, heterophile antibodies, antitroponin antibodies, and macrotroponin complexes can be observed both in seemingly healthy individuals and patients with cardiac diseases, potentially leading to false positive or disproportionate elevation of cTn (cardiac troponin) assay results and introducing discrepancies in clinical interpretations with impact on medical management. In this review article, we describe the possible mechanisms of cTn release and the sources of variations in the assessment of circulating cTn levels.

View Article and Find Full Text PDF

Whether single-cell RNA-sequencing (scRNA-seq) captures the same biological information as single-nucleus RNA-sequencing (snRNA-seq) remains uncertain and likely to be context-dependent. Herein, a head-to-head comparison was performed in matched normal-adenocarcinoma human lung samples to assess biological insights derived from scRNA-seq versus snRNA-seq and better understand the cellular transition that occurs from normal to tumoral tissue. Here, the transcriptome of 160,621 cells/nuclei was obtained.

View Article and Find Full Text PDF

Background: Carriers of the E40K loss-of-function variant in Angiopoietin-like 4 (ANGPTL4), have lower plasma triglyceride levels as well as lower rates of coronary artery disease (CAD) and type 2 diabetes (T2D). These genetic data suggest ANGPTL4 inhibition as a potential therapeutic target for cardiometabolic diseases. However, it is unknown whether the association between E40K and human diseases is due to linkage disequilibrium confounding.

View Article and Find Full Text PDF

Although both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discover 22 novel gene-sleep duration interaction loci for blood pressure, mapped to genes involved in neurological, thyroidal, bone metabolism, and hematopoietic pathways.

View Article and Find Full Text PDF

There is currently no medical therapy to prevent calcific aortic valve stenosis (CAVS). Multi-omics approaches could lead to the identification of novel molecular targets. Here, we perform a genome-wide association study (GWAS) meta-analysis including 14,819 cases among 941,863 participants of European ancestry.

View Article and Find Full Text PDF

As the demand for bacteriophage (phage) therapy increases due to antibiotic resistance in microbial pathogens, strategies and methods for increased efficiency, large-scale phage production need to be determined. To date, very little has been published on how to establish scalable production for phages, while achieving and maintaining a high titer in an economical manner. The present work outlines a phage production strategy using an enterotoxigenic Escherichia coli-targeting phage, 'Phage75', and accounts for the following variables: infection load, multiplicity of infection, temperature, media composition, harvest time, and host bacteria.

View Article and Find Full Text PDF
Article Synopsis
  • Researchers are exploring therapies targeting ANGPTL3 to lower lipoprotein-lipid levels and reduce the risk of cardiovascular diseases.
  • The study employed Mendelian randomisation to assess how genetic variations affect ANGPTL3 expression and their potential impact on triglyceride and apoB levels, as well as various heart-related conditions.
  • Results showed that common genetic variants significantly lowered plasma triglyceride levels, while having minimal effects on LDL cholesterol and no impact on coronary artery disease or other cardiometabolic diseases.
View Article and Find Full Text PDF

Background: Lp(a) (lipoprotein[a]) is a highly atherogenic lipoprotein subfraction that may contribute to polygenic risk of coronary artery disease (CAD), but the extent of this contribution is unknown. Our objective was to estimate the contribution of Lp(a) to polygenic risk of CAD and to evaluate the respective contributions of Lp(a) and a CAD polygenic risk score (PRS) to CAD.

Methods: A total of 372 385 UK Biobank participants of European ancestry free of CAD at baseline were included.

View Article and Find Full Text PDF

Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent disease with no specific drug therapy. High-throughput metabolomics present an unprecedented opportunity to identify biomarkers and potentially causal risk factors for NAFLD. Here, we determined the impact of 21 circulating metabolites, 17 lipids, and 132 lipoprotein particle characteristics on NAFLD combining prospective observational and two-sample Mendelian randomization (MR) analyses in 121,032 UK Biobank participants.

View Article and Find Full Text PDF

Background: Biofilm formation is a major clinical challenge contributing to treatment failure of periprosthetic joint infection (PJI). Lytic bacteriophages (phages) can target biofilm associated bacteria at localized sites of infection. The aim of this study is to investigate whether combination therapy of phage and vancomycin is capable of clearing biofilm-like aggregates formed in human synovial fluid.

View Article and Find Full Text PDF

Background The impact of an elevated body mass index (BMI) on atherosclerotic cardiovascular disease (ASCVD) risk in individuals who are metabolically healthy is debated. We investigated the respective contributions of BMI as well as lifestyle and cardiometabolic risk factors combined to ASCVD incidence in 319 866 UK Biobank participants. Methods and Results We developed a cardiovascular health score (CVHS) based on 4 lifestyle and 6 cardiometabolic parameters.

View Article and Find Full Text PDF

Aims: Elevated lipoprotein(a) [Lp(a)] levels are associated with the risk of coronary artery disease (CAD) and calcific aortic valve stenosis (CAVS). Observational studies revealed that Lp(a) and C-reactive protein (CRP) levels, a biomarker of systemic inflammation, may jointly predict CAD risk. Whether Lp(a) and CRP levels also jointly predict CAVS incidence and progression is unknown.

View Article and Find Full Text PDF
Article Synopsis
  • * Findings highlight important pathways connected to heart development, muscle contraction, and overall heart health related to these angles.
  • * The research also shows genetic links between QRS-T angles and various heart conditions like atrial fibrillation and blockages, suggesting potential areas for future research and risk assessments in cardiovascular health.
View Article and Find Full Text PDF