A5007653975- Genetic Associations and Epidemiology
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Bioinformatics and Genomic Networks
- Cancer-related molecular mechanisms research
- Adipose Tissue and Metabolism
- Cell Adhesion Molecules Research
- MicroRNA in disease regulation
- Lipid metabolism and disorders
- Genomics and Rare Diseases
- Adipokines, Inflammation, and Metabolic Diseases
- Cancer-related gene regulation
- Atherosclerosis and Cardiovascular Diseases
- Nutrition and Health in Aging
- Hormonal Regulation and Hypertension
- RNA Research and Splicing
- Lipoproteins and Cardiovascular Health
- Nutrition, Genetics, and Disease
- Genetic Mapping and Diversity in Plants and Animals
- Health, Environment, Cognitive Aging
- Diet and metabolism studies
- TGF-β signaling in diseases
- Immune cells in cancer
- Pancreatic function and diabetes
- Cholesterol and Lipid Metabolism
University of Ottawa
2015-2024
Canadian Heart Research Centre
2014-2021
Technical University of Denmark
2016
Karolinska University Hospital
2016
Center for Human Genetics
2013
Amsterdam UMC Location University of Amsterdam
2013
Centre Hospitalier de l’Université de Montréal
2012
Genome-wide association studies have so far identified 56 loci associated with risk of coronary artery disease (CAD). Many CAD show pleiotropy; that is, they are also other diseases or traits. This study sought to systematically test if genetic variants for non-CAD diseases/traits associate and undertake a comprehensive analysis the extent pleiotropy all loci. In discovery analyses involving 42,335 cases 78,240 control subjects we tested 29,383 common (minor allele frequency >5%) single...
To investigate potential cardiovascular and other effects of long-term pharmacological interleukin 1 (IL-1) inhibition, we studied genetic variants that produce inhibition IL-1, a master regulator inflammation. We created score combining the alleles two common (rs6743376 rs1542176) are located upstream IL1RN, gene encoding IL-1 receptor antagonist (IL-1Ra; an endogenous inhibitor both IL-1α IL-1β); increase soluble IL-1Ra protein concentration. compared on inflammation biomarkers this with...
To identify genetic variants that have a regulatory impact on circulating microRNAs (miRNAs) and to connect risk blood traits/biomarkers through the miRNAs.Leveraging miRNA-Seq data 1000 Genomes imputed genotypes, we carried out genome-wide association analysis for SNPs regulate expression of miRNAs in sample 710 unrelated subjects European ancestry. Wherever possible, used from Framingham Geuvadis studies replicate our findings. We found at least one significant (P < 5e-8) miRNA-eQTL...
Objective— A recent genome-wide association study meta-analysis identified an intronic single nucleotide polymorphism in SMAD3 , rs56062135C>T, the minor allele (T) which associates with protection from coronary artery disease. Relevant to atherosclerosis, is a key contributor transforming growth factor-β pathway signaling. Here, we seek identify ≥1 causal disease–associated polymorphisms at locus and characterize mechanisms whereby risk allele(s) contribute disease risk. Approach...
Background The TRIB 1 locus has been linked to hepatic triglyceride metabolism in mice and plasma triglycerides coronary artery disease humans. lipid‐associated single nucleotide polymorphisms ( SNP s), identified by genome‐wide association studies, are located ≈30 kb downstream from 1, suggesting complex regulatory effects on genes or pathways relevant metabolism. goal of this study was investigate the functional relationship between common s at lipid traits. Methods Results...
Links between substance use habits, obesity, stress and the related cardiovascular outcomes can be, in part, because of loci with pleiotropic effects. To investigate this hypothesis, we performed genome-wide mapping 119 multigenerational families from a population Saguenay-Lac-St-Jean region known founder effect using 58 000 single-nucleotide polymorphisms 437 microsatellite markers to identify genetic components following factors: habitual alcohol, tobacco coffee use; response mental...
Recent genome-wide association studies have identified multiple loci robustly associated with plasma lipids, which also contribute to extreme lipid phenotypes. However, these common genetic variants explain <12% of variation in traits. Adiposity is an important determinant lipoproteins, particularly TGs and HDL cholesterol (HDLc) concentrations. Thus, interactions between genes clinical phenotypes may this unexplained heritability. We applied a weighted risk score (GRS) for both HDLc two...
With the availability of genome-wide genotype data from GWAS studies, it is now possible to compute genetic relatedness among individuals and estimate its contribution (SNP-based heritability) phenotypic variance using Mixed-Linear-Models (MLMs). The estimated heritability can be partitioned according biological features gain insight into architecture a disease. Here, we aimed examine structure coronary artery disease (CAD).We investigated CAD 3,163,082 autosomal SNPs (MAF ≥ 0.01) MLMs in...
Abstract Background Accelerated reproductive aging, in women indicated by early natural menopause, is associated with increased coronary heart disease (CHD) risk observational studies. Conversely, an adverse CHD profile has been suggested to accelerate menopause. Objectives To study the direction and evidence for causality of relationship between aging (non-)fatal factors a bidirectional Mendelian randomization (MR) approach, using age at menopause (ANM) genetic variants as measure...
There is ongoing controversy as to whether obesity confers risk for CAD independently of associated factors including diabetes mellitus. We have carried out a Mendelian randomization study using genetic score (GRS) body mass index (BMI) based on 35 alleles investigate this question in population 5831 early onset cases without mellitus and 3832 elderly healthy control subjects, all strictly European ancestry, with adjustment traditional (TRFs). then estimated the correlation between these BMI...
Background and aimsA recently identified locus for coronary artery disease (CAD) tagged by rs8042271 is in a region of tight linkage disequilibrium (LD) between 2 genes (MFGE8, ABHD2) previously linked to atherosclerosis. Here we have explored the regulatory framework this identify its functional relationship CAD.MethodsThe CAD Associated Region MFGE8 ABHD2 (CARMA) was investigated bioinformatic approaches transcriptional reporter assays prioritize target putative causal variants. Findings...
The objective of this study is to investigate the extent and nature pleiotropy between coronary artery disease (CAD) body mass index (BMI).We examined contribution genome-wide single-nucleotide polymorphisms (minor allele frequency ≥0.01) co-occurrence CAD BMI in a sample genetically unrelated 8041 subjects (genetic resemblance ≤0.025) European ancestry using mixed-linear-models. We further partitioned estimated according biological features gain insight into BMI.We found significant...
Previous high throughput screening studies indicated trans-eQTLs tend to be tissue specific. In this study, I probed if feature can used identify tissue-specific gene regulatory networks. eQTL data (P&lt;5e-8) for 16,259 genes were identified and their summary association statistics obtained from the eQTLGene database. Next, eQTLs that display both cis trans effects selected between corresponding examined using Mendelian randomization. A total of 169 exerted trans-regulatory impacts on...
Inter-individual variability in weight loss during obesity treatment is complex and poorly understood. Here we use whole body tissue approaches to investigate fuel oxidation characteristics skeletal muscle fibers, cells distinct circulating protein biomarkers before after a high fat meal (HFM) challenge those who lost the most (obese diet-sensitive; ODS) vs least diet-resistant; ODR) amount of highly controlled management program. In 20 stable-matched ODS ODR women previously completed...
Here, we performed a genome-wide search for methylation sites that contribute to the risk of obesity. We integrated quantitative trait locus (mQTL) data with BMI GWAS information through SNP-based multiomics approach identify genomic regions where mQTLs site co-localize obesity SNPs. then tested whether identified contributed Mendelian randomization. multiple causally contributing validated these findings replication stage. By integrating expression (eQTL) data, noted lower at cg21178254...
In this study, we aimed to investigate functional mechanisms underlying coronary artery disease (CAD) loci and find molecular biomarkers for CAD.We devised a multiomics data analysis approach based on Mendelian randomization utilized it search causally associated with the risk of CAD within genomic regions known be CAD.Through our CAD-centered approach, identified 33 (probes) that were CAD. The majority these (N=19) methylation probes; moreover, was often behind causal effect...
Fibronectin (FN1) is an essential regulator of homodynamic processes and tissue remodeling that have been proposed to contribute atherosclerosis. Moreover, recent large-scale genome-wide association studies (GWAS) linked common genetic variants within the FN1 gene coronary artery disease risk.Public databases were analyzed by 2-Sample Mendelian Randomization. Expression constructs encoding short reporter full-length plasma introduced in various cell models. Secreted cellular levels then...