Search

Your search keyword '"Dubé, Marie‐Pierre"' showing total 473 results
Start Over Author "Dubé, Marie‐Pierre" Search Limiters Available in Library Collection
473 results on '"Dubé, Marie‐Pierre"'

1. The role of genetically predicted serum iron levels on neurodegenerative and cardiovascular traits

Author

Belbellaj, Wiame, Lona-Durazo, Frida, Bodano, Cinzia, Busseuil, David, Cyr, Marie-Christyne, Fiorillo, Edoardo, Mulas, Antonella, Provost, Sylvie, Steri, Maristella, Tanaka, Toshiko, Vanderwerff, Brett, Wang, Jiongming, Byrne, Ross P., Cucca, Francesco, Dubé, Marie-Pierre, Ferrucci, Luigi, McLaughlin, Russell L., Tardif, Jean-Claude, Zawistowski, Matthew, and Gagliano Taliun, Sarah A.

Published
2024
Full Text
View/download PDF

2. GWAS of CRP response to statins further supports the role of APOE in statin response: A GIST consortium study

Author

Magavern, Emma F., Deshmukh, Harshal, Asselin, Geraldine, Theusch, Elizabeth, Trompet, Stella, Li, Xiaohui, Noordam, Raymond, Chen, Y.-D. Ida, Seeman, Teresa E., Taylor, Kent D., Post, Wendy S., Tardif, Jean-Claude, Paul, Dirk S., Benjamin, Emelia J., Heard-Costa, Nancy L., Vasan, Ramachandran S., Rotter, Jerome I., Krauss, Ronald M., Jukema, J.Wouter, Ridker, Paul M., Munroe, Patricia B., Caulfield, Mark J., Chasman, Daniel I., Dubé, Marie-Pierre, Hitman, Graham A., and Warren, Helen R.

Published
2025
Full Text
View/download PDF

4. Pharmacogenetics-guided dalcetrapib therapy after an acute coronary syndrome: the dal-GenE trial

Author

Tardif, Jean Claude, Pfeffer, Marc A, Kouz, Simon, Koenig, Wolfgang, Maggioni, Aldo P, McMurray, John JV, Mooser, Vincent, Waters, David D, Grégoire, Jean C, L’Allier, Philippe L, Jukema, J Wouter, White, Harvey D, Heinonen, Therese, Black, Donald M, Laghrissi-Thode, Fouzia, Levesque, Sylvie, Guertin, Marie Claude, Dubé, Marie Pierre, and Investigators, for the dal-GenE

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Clinical Trials and Supportive Activities, Clinical Research, Cardiovascular, Genetics, Heart Disease - Coronary Heart Disease, Heart Disease, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Good Health and Well Being, Acute Coronary Syndrome, Adenylyl Cyclases, Amides, Anticholesteremic Agents, Double-Blind Method, Esters, Heart Arrest, Humans, Myocardial Infarction, Pharmacogenetics, Retrospective Studies, Stroke, Sulfhydryl Compounds, Precision medicine, Atherosclerosis, Myocardial infarction, CETP, Adenylate cyclase type 9, dal-GenE Investigators, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Clinical sciences
Abstract

AimsIn a retrospective analysis of dal-Outcomes, the effect of dalcetrapib on cardiovascular events was influenced by an adenylate cyclase type 9 (ADCY9) gene polymorphism. The dal-GenE study was conducted to test this pharmacogenetic hypothesis.Methods and resultsdal-GenE was a double-blind trial in patients with an acute coronary syndrome within 1-3 months and the AA genotype at variant rs1967309 in the ADCY9 gene. A total of 6147 patients were randomly assigned to receive dalcetrapib 600 mg or placebo daily. The primary endpoint was the time from randomization to first occurrence of cardiovascular death, resuscitated cardiac arrest, non-fatal myocardial infarction, or non-fatal stroke. After a median follow-up of 39.9 months, the primary endpoint occurred in 292 (9.5%) of 3071 patients in the dalcetrapib group and 327 (10.6%) of 3076 patients in the placebo group [hazard ratio 0.88; 95% confidence interval (CI) 0.75-1.03; P = 0.12]. The hazard ratios for the components of the primary endpoint were 0.79 (95% CI 0.65-0.96) for myocardial infarction, 0.92 (95% CI 0.64-1.33) for stroke, 1.21 (95% CI 0.91-1.60) for death from cardiovascular causes, and 2.33 (95% CI 0.60-9.02) for resuscitated cardiac arrest. In a pre-specified on-treatment sensitivity analysis, the primary endpoint event rate was 7.8% (236/3015) in the dalcetrapib group and 9.3% (282/3031) in the placebo group (hazard ratio 0.83; 95% CI 0.70-0.98).ConclusionDalcetrapib did not significantly reduce the risk of occurrence of the primary endpoint of ischaemic cardiovascular events at end of study. A new trial would be needed to test the pharmacogenetic hypothesis that dalcetrapib improves the prognosis of patients with the AA genotype.Clinical trial registrationTrial registration dal-GenE ClinicalTrials.gov Identifier: NCT02525939.

Published
2022

5. Deep interpretability for GWAS

Author

Sharma, Deepak, Durand, Audrey, Legault, Marc-André, Perreault, Louis-Philippe Lemieux, Lemaçon, Audrey, Dubé, Marie-Pierre, and Pineau, Joelle

Subjects
Computer Science - Machine Learning, Quantitative Biology - Genomics, Statistics - Applications, Statistics - Machine Learning
Abstract

Genome-Wide Association Studies are typically conducted using linear models to find genetic variants associated with common diseases. In these studies, association testing is done on a variant-by-variant basis, possibly missing out on non-linear interaction effects between variants. Deep networks can be used to model these interactions, but they are difficult to train and interpret on large genetic datasets. We propose a method that uses the gradient based deep interpretability technique named DeepLIFT to show that known diabetes genetic risk factors can be identified using deep models along with possibly novel associations., Comment: Accepted at ICML 2020 workshop on ML Interpretability for Scientific Discovery

Published
2020

7. Role of Adenylate Cyclase 9 in the Pharmacogenomic Response to Dalcetrapib: Clinical Paradigm and Molecular Mechanisms in Precision Cardiovascular Medicine.

Author

Rhainds, David, Packard, Chris J, Brodeur, Mathieu R, Niesor, Eric J, Sacks, Frank M, Jukema, J Wouter, Wright, R Scott, Waters, David D, Heinonen, Therese, Black, Donald M, Laghrissi-Thode, Fouzia, Dubé, Marie-Pierre, Pfeffer, Marc A, and Tardif, Jean-Claude

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Rare Diseases, Clinical Research, Human Genome, Genetics, Cardiovascular, Good Health and Well Being, Adenylyl Cyclases, Amides, Biomarkers, Cardiovascular Diseases, Cholesterol, Cholesterol Ester Transfer Proteins, Esters, Genotype, Humans, Pharmacogenetics, Precision Medicine, Sulfhydryl Compounds, acute coronary syndrome, adenylate cyclase, dalcetrapib, macrophages, precision medicine, Medical Biotechnology, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

Following the neutral results of the dal-OUTCOMES trial, a genome-wide study identified the rs1967309 variant in the adenylate cyclase type 9 (ADCY9) gene on chromosome 16 as being associated with the risk of future cardiovascular events only in subjects taking dalcetrapib, a CETP (cholesterol ester transfer protein) modulator. Homozygotes for the minor A allele (AA) were protected from recurrent cardiovascular events when treated with dalcetrapib, while homozygotes for the major G allele (GG) had increased risk. Here, we present the current state of knowledge regarding the impact of rs1967309 in ADCY9 on clinical observations and biomarkers in dalcetrapib trials and the effects of mouse ADCY9 gene inactivation on cardiovascular physiology. Finally, we present our current model of the interaction between dalcetrapib and ADCY9 gene variants in the arterial wall macrophage, based on the intracellular role of CETP in the transfer of complex lipids from endoplasmic reticulum membranes to lipid droplets. Briefly, the concept is that dalcetrapib would inhibit CETP-mediated transfer of cholesteryl esters, resulting in a progressive inhibition of cholesteryl ester synthesis and free cholesterol accumulation in the endoplasmic reticulum. Reduced ADCY9 activity, by paradoxically leading to higher cyclic AMP levels and in turn increased cellular cholesterol efflux, could impart cardiovascular protection in rs1967309 AA patients. The ongoing dal-GenE trial recruited 6145 patients with the protective AA genotype and will provide a definitive answer to whether dalcetrapib will be protective in this population.

Published
2021

8. Pharmacogenomics of the Efficacy and Safety of Colchicine in COLCOT

Author

Dubé, Marie-Pierre, Legault, Marc-André, Lemaçon, Audrey, Perreault, Louis-Philippe Lemieux, Fouodjio, René, Waters, David D, Kouz, Simon, Pinto, Fausto J, Maggioni, Aldo P, Diaz, Rafael, Berry, Colin, Koenig, Wolfgang, Lopez-Sendon, Jose, Gamra, Habib, Kiwan, Ghassan S, Asselin, Géraldine, Provost, Sylvie, Barhdadi, Amina, Sun, Maxine, Cossette, Mariève, Blondeau, Lucie, Mongrain, Ian, Dubois, Anick, Rhainds, David, Bouabdallaoui, Nadia, Samuel, Michelle, de Denus, Simon, L’Allier, Philippe L, Guertin, Marie-Claude, Roubille, François, and Tardif, Jean-Claude

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Human Genome, Clinical Research, Heart Disease, Digestive Diseases, Cardiovascular, Patient Safety, Genetics, Clinical Trials and Supportive Activities, Heart Disease - Coronary Heart Disease, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Aged, Cardiovascular Diseases, Colchicine, Female, Gastrointestinal Diseases, Genome-Wide Association Study, Genotype, Humans, Male, Middle Aged, Pharmacogenetics, Phosphotransferases, Placebo Effect, Polymorphism, Single Nucleotide, Proportional Hazards Models, Randomized Controlled Trials as Topic, Treatment Outcome, acute coronary syndrome, colchicine, gastrointestinal diseases, myocardial infarction, pharmacogenetics, Medical Biotechnology, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

BackgroundThe randomized, placebo-controlled COLCOT (Colchicine Cardiovascular Outcomes Trial) has shown the benefits of colchicine 0.5 mg daily to lower the rate of ischemic cardiovascular events in patients with a recent myocardial infarction. Here, we conducted a post hoc pharmacogenomic study of COLCOT with the aim to identify genetic predictors of the efficacy and safety of treatment with colchicine.MethodsThere were 1522 participants of European ancestry from the COLCOT trial available for the pharmacogenomic study of COLCOT trial. The pharmacogenomic study's primary cardiovascular end point was defined as for the main trial, as time to first occurrence of cardiovascular death, resuscitated cardiac arrest, myocardial infarction, stroke, or urgent hospitalization for angina requiring coronary revascularization. The safety end point was time to the first report of gastrointestinal events. Patients' DNA was genotyped using the Illumina Global Screening array followed by imputation. We performed a genome-wide association study in colchicine-treated patients.ResultsNone of the genetic variants passed the genome-wide association study significance threshold for the primary cardiovascular end point conducted in 702 patients in the colchicine arm who were compliant to medication. The genome-wide association study for gastrointestinal events was conducted in all 767 patients in the colchicine arm and found 2 significant association signals, one with lead variant rs6916345 (hazard ratio, 1.89 [95% CI, 1.52-2.35], P=7.41×10-9) in a locus which colocalizes with Crohn disease, and one with lead variant rs74795203 (hazard ratio, 2.51 [95% CI, 1.82-3.47]; P=2.70×10-8), an intronic variant in gene SEPHS1. The interaction terms between the genetic variants and treatment with colchicine versus placebo were significant.ConclusionsWe found 2 genomic regions associated with gastrointestinal events in patients treated with colchicine. Those findings will benefit from replication to confirm that some patients may have genetic predispositions to lower tolerability of treatment with colchicine.

Published
2021

9. Time-to-treatment initiation of colchicine and cardiovascular outcomes after myocardial infarction in the Colchicine Cardiovascular Outcomes Trial (COLCOT)

Author

Bouabdallaoui, Nadia, Tardif, Jean-Claude, Waters, David D, Pinto, Fausto J, Maggioni, Aldo P, Diaz, Rafael, Berry, Colin, Koenig, Wolfgang, Lopez-Sendon, Jose, Gamra, Habib, Kiwan, Ghassan S, Blondeau, Lucie, Orfanos, Andreas, Ibrahim, Reda, Grégoire, Jean C, Dubé, Marie-Pierre, Samuel, Michelle, Morel, Olivier, Lim, Pascal, Bertrand, Olivier F, Kouz, Simon, Guertin, Marie-Claude, L’Allier, Philippe L, and Roubille, Francois

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Heart Disease - Coronary Heart Disease, Brain Disorders, Cardiovascular, Clinical Trials and Supportive Activities, Clinical Research, Heart Disease, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Angina Pectoris, Colchicine, Humans, Myocardial Infarction, Stroke, Time-to-Treatment, Treatment Outcome, COLCOT, Cardiovascular inflammation, Inflammasome, Time-to-treatment initiation, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Clinical sciences
Abstract

AimsThe COLchicine Cardiovascular Outcomes Trial (COLCOT) demonstrated the benefits of targeting inflammation after myocardial infarction (MI). We aimed to determine whether time-to-treatment initiation (TTI) influences the beneficial impact of colchicine.Methods and resultsIn COLCOT, patients were randomly assigned to receive colchicine or placebo within 30 days post-MI. Time-to-treatment initiation was defined as the length of time between the index MI and the initiation of study medication. The primary efficacy endpoint was a composite of cardiovascular death, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina requiring coronary revascularization. The relationship between endpoints and various TTI (8 days) was examined using multivariable Cox regression models. Amongst the 4661 patients included in this analysis, there were 1193, 720, and 2748 patients, respectively, in the three TTI strata. After a median follow-up of 22.7 months, there was a significant reduction in the incidence of the primary endpoint for patients in whom colchicine was initiated < Day 3 compared with placebo [hazard ratios (HR) = 0.52, 95% confidence intervals (CI) 0.32-0.84], in contrast to patients in whom colchicine was initiated between Days 4 and 7 (HR = 0.96, 95% CI 0.53-1.75) or > Day 8 (HR = 0.82, 95% CI 0.61-1.11). The beneficial effects of early initiation of colchicine were also demonstrated for urgent hospitalization for angina requiring revascularization (HR = 0.35), all coronary revascularization (HR = 0.63), and the composite of cardiovascular death, resuscitated cardiac arrest, MI, or stroke (HR = 0.55, all P

Published
2020

10. Study design of Dal-GenE, a pharmacogenetic trial targeting reduction of cardiovascular events with dalcetrapib

Author

Tardif, Jean-Claude, Dubé, Marie-Pierre, Pfeffer, Marc A, Waters, David D, Koenig, Wolfgang, Maggioni, Aldo P, McMurray, John JV, Mooser, Vincent, White, Harvey D, Heinonen, Therese, Black, Donald M, Guertin, Marie-Claude, and Investigators, for the dal-GenE

Subjects
Genetics, Heart Disease - Coronary Heart Disease, Heart Disease, Cardiovascular, Prevention, Clinical Research, Clinical Trials and Supportive Activities, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Good Health and Well Being, Adenylyl Cyclases, Amides, Anticholesteremic Agents, Atherosclerosis, Dose-Response Relationship, Drug, Double-Blind Method, Esters, Female, Follow-Up Studies, Genetic Testing, Genome-Wide Association Study, Genotype, Global Health, Humans, Incidence, Male, Middle Aged, Pharmacogenetics, Polymorphism, Genetic, Precision Medicine, Prognosis, Prospective Studies, Retrospective Studies, Sulfhydryl Compounds, dal-GenE Investigators, Cardiorespiratory Medicine and Haematology, Public Health and Health Services, Cardiovascular System & Hematology
Abstract

The objectives of precision medicine are to better match patient characteristics with the therapeutic intervention to optimize the chances of beneficial actions while reducing the exposure to unneeded adverse drug experiences. In a retrospective genome-wide association study of the overall neutral placebo-controlled dal-Outcomes trial, the effect of the cholesteryl ester transfer protein (CETP) modulator dalcetrapib on the composite of cardiovascular death, myocardial infarction or stroke was found to be influenced by a polymorphism in the adenylate cyclase type 9 (ADCY9) gene. Whereas patients with the AA genotype at position rs1967309 experienced fewer cardiovascular events with dalcetrapib, those with the GG genotype had an increased rate and the heterozygous AG genotype exhibited no difference from placebo. Measurements of cholesterol efflux and C-reactive protein (CRP) offered directionally supportive genotype-specific findings. In a separate, smaller, placebo-controlled trial, regression of ultrasonography-determined carotid intimal-medial thickness was only observed in dalcetrapib-treated patients with the AA genotype. Collectively, these observations led to the hypothesis that the cardiovascular effects of dalcetrapib may be pharmacogenetically determined, with a favorable benefit-risk ratio only for patients with this specific genotype. We describe below the design of dal-GenE, a precision medicine, placebo-controlled clinical outcome trial of dalcetrapib in patients with a recent acute myocardial infarction with the unique feature of selecting only those with the AA genotype at rs1967309 in the ADCY9 gene.

Published
2020

13. Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction.

Author

Tardif, Jean-Claude, Kouz, Simon, Waters, David D, Bertrand, Olivier F, Diaz, Rafael, Maggioni, Aldo P, Pinto, Fausto J, Ibrahim, Reda, Gamra, Habib, Kiwan, Ghassan S, Berry, Colin, López-Sendón, José, Ostadal, Petr, Koenig, Wolfgang, Angoulvant, Denis, Grégoire, Jean C, Lavoie, Marc-André, Dubé, Marie-Pierre, Rhainds, David, Provencher, Mylène, Blondeau, Lucie, Orfanos, Andreas, L'Allier, Philippe L, Guertin, Marie-Claude, and Roubille, François

Subjects
Humans, Cardiovascular Diseases, Angina Pectoris, Myocardial Infarction, Recurrence, Colchicine, C-Reactive Protein, Anti-Inflammatory Agents, Incidence, Proportional Hazards Models, Double-Blind Method, Aged, Middle Aged, Female, Male, Stroke, Intention to Treat Analysis, Kaplan-Meier Estimate, Percutaneous Coronary Intervention, Biomarkers, General & Internal Medicine, Medical and Health Sciences
Abstract

BackgroundExperimental and clinical evidence supports the role of inflammation in atherosclerosis and its complications. Colchicine is an orally administered, potent antiinflammatory medication that is indicated for the treatment of gout and pericarditis.MethodsWe performed a randomized, double-blind trial involving patients recruited within 30 days after a myocardial infarction. The patients were randomly assigned to receive either low-dose colchicine (0.5 mg once daily) or placebo. The primary efficacy end point was a composite of death from cardiovascular causes, resuscitated cardiac arrest, myocardial infarction, stroke, or urgent hospitalization for angina leading to coronary revascularization. The components of the primary end point and safety were also assessed.ResultsA total of 4745 patients were enrolled; 2366 patients were assigned to the colchicine group, and 2379 to the placebo group. Patients were followed for a median of 22.6 months. The primary end point occurred in 5.5% of the patients in the colchicine group, as compared with 7.1% of those in the placebo group (hazard ratio, 0.77; 95% confidence interval [CI], 0.61 to 0.96; P = 0.02). The hazard ratios were 0.84 (95% CI, 0.46 to 1.52) for death from cardiovascular causes, 0.83 (95% CI, 0.25 to 2.73) for resuscitated cardiac arrest, 0.91 (95% CI, 0.68 to 1.21) for myocardial infarction, 0.26 (95% CI, 0.10 to 0.70) for stroke, and 0.50 (95% CI, 0.31 to 0.81) for urgent hospitalization for angina leading to coronary revascularization. Diarrhea was reported in 9.7% of the patients in the colchicine group and in 8.9% of those in the placebo group (P = 0.35). Pneumonia was reported as a serious adverse event in 0.9% of the patients in the colchicine group and in 0.4% of those in the placebo group (P = 0.03).ConclusionsAmong patients with a recent myocardial infarction, colchicine at a dose of 0.5 mg daily led to a significantly lower risk of ischemic cardiovascular events than placebo. (Funded by the Government of Quebec and others; COLCOT ClinicalTrials.gov number, NCT02551094.).

Published
2019

14. Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution

Author

Justice, Anne E, Karaderi, Tugce, Highland, Heather M, Young, Kristin L, Graff, Mariaelisa, Lu, Yingchang, Turcot, Valérie, Auer, Paul L, Fine, Rebecca S, Guo, Xiuqing, Schurmann, Claudia, Lempradl, Adelheid, Marouli, Eirini, Mahajan, Anubha, Winkler, Thomas W, Locke, Adam E, Medina-Gomez, Carolina, Esko, Tõnu, Vedantam, Sailaja, Giri, Ayush, Lo, Ken Sin, Alfred, Tamuno, Mudgal, Poorva, Ng, Maggie CY, Heard-Costa, Nancy L, Feitosa, Mary F, Manning, Alisa K, Willems, Sara M, Sivapalaratnam, Suthesh, Abecasis, Goncalo, Alam, Dewan S, Allison, Matthew, Amouyel, Philippe, Arzumanyan, Zorayr, Balkau, Beverley, Bastarache, Lisa, Bergmann, Sven, Bielak, Lawrence F, Blüher, Matthias, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Böger, Carsten A, Bork-Jensen, Jette, Bottinger, Erwin P, Bowden, Donald W, Brandslund, Ivan, Broer, Linda, Burt, Amber A, Butterworth, Adam S, Caulfield, Mark J, Cesana, Giancarlo, Chambers, John C, Chasman, Daniel I, Chen, Yii-Der Ida, Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y, Collins, Francis S, Cook, James P, Cox, Amanda J, Crosslin, David S, Danesh, John, de Bakker, Paul IW, Denus, Simon de, Mutsert, Renée de, Dedoussis, George, Demerath, Ellen W, Dennis, Joe G, Denny, Josh C, Di Angelantonio, Emanuele, Dörr, Marcus, Drenos, Fotios, Dubé, Marie-Pierre, Dunning, Alison M, Easton, Douglas F, Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki-Eleni, Feng, Shuang, Ferrannini, Ele, Ferrieres, Jean, Florez, Jose C, Fornage, Myriam, Fox, Caroline S, Franks, Paul W, Friedrich, Nele, Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Giedraitis, Vilmantas, Girotto, Giorgia, Gorski, Mathias, Grallert, Harald, Grarup, Niels, Grove, Megan L, Gustafsson, Stefan, Haessler, Jeff, Hansen, Torben, and Hattersley, Andrew T

Subjects
Clinical Research, Obesity, Genetics, Nutrition, Prevention, Biotechnology, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Metabolic and endocrine, Cardiovascular, Animals, Body Fat Distribution, Body Mass Index, Case-Control Studies, Drosophila, Exome, Female, Gene Frequency, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Homeostasis, Humans, Lipids, Male, Proteins, Risk Factors, Waist-Hip Ratio, CHD Exome+ Consortium, Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, EPIC-CVD Consortium, ExomeBP Consortium, Global Lipids Genetic Consortium, GoT2D Genes Consortium, InterAct, ReproGen Consortium, T2D-Genes Consortium, MAGIC Investigators, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF

Published
2019

16. Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity.

Author

Turcot, Valérie, Lu, Yingchang, Highland, Heather M, Schurmann, Claudia, Justice, Anne E, Fine, Rebecca S, Bradfield, Jonathan P, Esko, Tõnu, Giri, Ayush, Graff, Mariaelisa, Guo, Xiuqing, Hendricks, Audrey E, Karaderi, Tugce, Lempradl, Adelheid, Locke, Adam E, Mahajan, Anubha, Marouli, Eirini, Sivapalaratnam, Suthesh, Young, Kristin L, Alfred, Tamuno, Feitosa, Mary F, Masca, Nicholas GD, Manning, Alisa K, Medina-Gomez, Carolina, Mudgal, Poorva, Ng, Maggie CY, Reiner, Alex P, Vedantam, Sailaja, Willems, Sara M, Winkler, Thomas W, Abecasis, Gonçalo, Aben, Katja K, Alam, Dewan S, Alharthi, Sameer E, Allison, Matthew, Amouyel, Philippe, Asselbergs, Folkert W, Auer, Paul L, Balkau, Beverley, Bang, Lia E, Barroso, Inês, Bastarache, Lisa, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F, Blüher, Matthias, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Böger, Carsten A, Bork-Jensen, Jette, Bots, Michiel L, Bottinger, Erwin P, Bowden, Donald W, Brandslund, Ivan, Breen, Gerome, Brilliant, Murray H, Broer, Linda, Brumat, Marco, Burt, Amber A, Butterworth, Adam S, Campbell, Peter T, Cappellani, Stefania, Carey, David J, Catamo, Eulalia, Caulfield, Mark J, Chambers, John C, Chasman, Daniel I, Chen, Yii-Der I, Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y, Cocca, Massimiliano, Collins, Francis S, Cook, James P, Corley, Janie, Corominas Galbany, Jordi, Cox, Amanda J, Crosslin, David S, Cuellar-Partida, Gabriel, D'Eustacchio, Angela, Danesh, John, Davies, Gail, Bakker, Paul IW, Groot, Mark CH, Mutsert, Renée, Deary, Ian J, Dedoussis, George, Demerath, Ellen W, Heijer, Martin, Hollander, Anneke I, Ruijter, Hester M, Dennis, Joe G, Denny, Josh C, Di Angelantonio, Emanuele, Drenos, Fotios, Du, Mengmeng, Dubé, Marie-Pierre, Dunning, Alison M, and Easton, Douglas F

Subjects
CHD Exome+ Consortium, EPIC-CVD Consortium, ExomeBP Consortium, Global Lipids Genetic Consortium, GoT2D Genes Consortium, EPIC InterAct Consortium, INTERVAL Study, ReproGen Consortium, T2D-Genes Consortium, MAGIC Investigators, Understanding Society Scientific Group, Nutrition, Obesity, Developmental Biology, Medical and Health Sciences, Biological Sciences
Abstract

In the version of this article originally published, one of the two authors with the name Wei Zhao was omitted from the author list and the affiliations for both authors were assigned to the single Wei Zhao in the author list. In addition, the ORCID for Wei Zhao (Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA) was incorrectly assigned to author Wei Zhou. The errors have been corrected in the HTML and PDF versions of the article.

Published
2018

17. Comprehensive genetic analysis of the human lipidome identifies loci associated with lipid homeostasis with links to coronary artery disease

Author

Cadby, Gemma, Giles, Corey, Melton, Phillip E., Huynh, Kevin, Mellett, Natalie A., Duong, Thy, Nguyen, Anh, Cinel, Michelle, Smith, Alex, Olshansky, Gavriel, Wang, Tingting, Brozynska, Marta, Inouye, Mike, McCarthy, Nina S., Ariff, Amir, Hung, Joseph, Hui, Jennie, Beilby, John, Dubé, Marie-Pierre, Watts, Gerald F., Shah, Sonia, Wray, Naomi R., Lim, Wei Ling Florence, Chatterjee, Pratishtha, Martins, Ian, Laws, Simon M., Porter, Tenielle, Vacher, Michael, Bush, Ashley I., Rowe, Christopher C., Villemagne, Victor L., Ames, David, Masters, Colin L., Taddei, Kevin, Arnold, Matthias, Kastenmüller, Gabi, Nho, Kwangsik, Saykin, Andrew J., Han, Xianlin, Kaddurah-Daouk, Rima, Martins, Ralph N., Blangero, John, Meikle, Peter J., and Moses, Eric K.

Published
2022
Full Text
View/download PDF

19. Diet Networks: Thin Parameters for Fat Genomics

Author

Romero, Adriana, Carrier, Pierre Luc, Erraqabi, Akram, Sylvain, Tristan, Auvolat, Alex, Dejoie, Etienne, Legault, Marc-André, Dubé, Marie-Pierre, Hussin, Julie G., and Bengio, Yoshua

Subjects
Computer Science - Learning, Statistics - Machine Learning
Abstract

Learning tasks such as those involving genomic data often poses a serious challenge: the number of input features can be orders of magnitude larger than the number of training examples, making it difficult to avoid overfitting, even when using the known regularization techniques. We focus here on tasks in which the input is a description of the genetic variation specific to a patient, the single nucleotide polymorphisms (SNPs), yielding millions of ternary inputs. Improving the ability of deep learning to handle such datasets could have an important impact in precision medicine, where high-dimensional data regarding a particular patient is used to make predictions of interest. Even though the amount of data for such tasks is increasing, this mismatch between the number of examples and the number of inputs remains a concern. Naive implementations of classifier neural networks involve a huge number of free parameters in their first layer: each input feature is associated with as many parameters as there are hidden units. We propose a novel neural network parametrization which considerably reduces the number of free parameters. It is based on the idea that we can first learn or provide a distributed representation for each input feature (e.g. for each position in the genome where variations are observed), and then learn (with another neural network called the parameter prediction network) how to map a feature's distributed representation to the vector of parameters specific to that feature in the classifier neural network (the weights which link the value of the feature to each of the hidden units). We show experimentally on a population stratification task of interest to medical studies that the proposed approach can significantly reduce both the number of parameters and the error rate of the classifier.

Published
2016

20. Identification of the genetic determinants responsible for retinal degeneration in families of Mexican descent

Author

Villanueva, Adda, Biswas, Pooja, Kishaba, Kameron, Suk, John, Tadimeti, Keerti, Raghavendra, Pongali B, Nadeau, Karine, Lamontagne, Bruno, Busque, Lambert, Geoffroy, Steve, Mongrain, Ian, Asselin, Géraldine, Provost, Sylvie, Dubé, Marie-Pierre, Nudleman, Eric, and Ayyagari, Radha

Subjects
Biomedical and Clinical Sciences, Ophthalmology and Optometry, Clinical Research, Genetic Testing, Neurodegenerative, Eye Disease and Disorders of Vision, Neurosciences, Genetics, Rare Diseases, Biotechnology, 2.1 Biological and endogenous factors, Eye, ATP-Binding Cassette Transporters, Adolescent, Adult, Aged, Child, Preschool, DNA Mutational Analysis, Extracellular Matrix Proteins, Eye Proteins, Female, Genetic Determinism, Genotyping Techniques, Humans, IMP Dehydrogenase, Male, Mexico, Middle Aged, Mutation, Pedigree, Phenotype, Retinal Degeneration, Exome Sequencing, cis-trans-Isomerases, Retinal degeneration, Mexican population, targeted sequencing, exome sequencing, ARRP, LCA, Opthalmology and Optometry, Ophthalmology & Optometry, Ophthalmology and optometry
Abstract

PurposeTo investigate the clinical characteristics and genetic basis of inherited retinal degeneration (IRD) in six unrelated pedigrees from Mexico.MethodsA complete ophthalmic evaluation including measurement of visual acuities, Goldman kinetic or Humphrey dynamic perimetry, Amsler test, fundus photography, and color vision testing was performed. Family history and blood samples were collected from available family members. DNA from members of two pedigrees was examined for known mutations using the APEX ARRP genotyping microarray and one pedigree using the APEX LCA genotyping microarray. The remaining three pedigrees were analyzed using a custom-designed targeted capture array covering the exons of 233 known retinal degeneration genes. Sequencing was performed on Illumina HiSeq. Reads were mapped against hg19, and variants were annotated using GATK and filtered by exomeSuite. Segregation and ethnicity-matched control sample analyses were performed by dideoxy sequencing.ResultsSix pedigrees with IRD were analyzed. Nine rare or novel, potentially pathogenic variants segregating with the phenotype were detected in IMPDH1, USH2A, RPE65, ABCA4, and FAM161A genes. Among these, six were known mutations while the remaining three changes in USH2A, RPE65, and FAM161A genes have not been previously reported to be associated with IRD. Analysis of 100 ethnicity-matched controls did not detect the presence of these three novel variants indicating, these are rare variants in the Mexican population.ConclusionsScreening patients diagnosed with IRD from Mexico identified six known mutations and three rare or novel potentially damaging variants in IMPDH1, USH2A, RPE65, ABCA4, and FAM161A genes that segregated with disease.

Published
2018

21. Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity

Author

Turcot, Valérie, Lu, Yingchang, Highland, Heather M, Schurmann, Claudia, Justice, Anne E, Fine, Rebecca S, Bradfield, Jonathan P, Esko, Tõnu, Giri, Ayush, Graff, Mariaelisa, Guo, Xiuqing, Hendricks, Audrey E, Karaderi, Tugce, Lempradl, Adelheid, Locke, Adam E, Mahajan, Anubha, Marouli, Eirini, Sivapalaratnam, Suthesh, Young, Kristin L, Alfred, Tamuno, Feitosa, Mary F, Masca, Nicholas GD, Manning, Alisa K, Medina-Gomez, Carolina, Mudgal, Poorva, Ng, Maggie CY, Reiner, Alex P, Vedantam, Sailaja, Willems, Sara M, Winkler, Thomas W, Abecasis, Gonçalo, Aben, Katja K, Alam, Dewan S, Alharthi, Sameer E, Allison, Matthew, Amouyel, Philippe, Asselbergs, Folkert W, Auer, Paul L, Balkau, Beverley, Bang, Lia E, Barroso, Inês, Bastarache, Lisa, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F, Blüher, Matthias, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Böger, Carsten A, Bork-Jensen, Jette, Bots, Michiel L, Bottinger, Erwin P, Bowden, Donald W, Brandslund, Ivan, Breen, Gerome, Brilliant, Murray H, Broer, Linda, Brumat, Marco, Burt, Amber A, Butterworth, Adam S, Campbell, Peter T, Cappellani, Stefania, Carey, David J, Catamo, Eulalia, Caulfield, Mark J, Chambers, John C, Chasman, Daniel I, Chen, Yii-Der I, Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y, Cocca, Massimiliano, Collins, Francis S, Cook, James P, Corley, Janie, Corominas Galbany, Jordi, Cox, Amanda J, Crosslin, David S, Cuellar-Partida, Gabriel, D’Eustacchio, Angela, Danesh, John, Davies, Gail, Bakker, Paul IW, Groot, Mark CH, Mutsert, Renée, Deary, Ian J, Dedoussis, George, Demerath, Ellen W, Heijer, Martin, Hollander, Anneke I, Ruijter, Hester M, Dennis, Joe G, Denny, Josh C, Di Angelantonio, Emanuele, Drenos, Fotios, Du, Mengmeng, Dubé, Marie-Pierre, Dunning, Alison M, and Easton, Douglas F

Subjects
Biological Sciences, Genetics, Nutrition, Human Genome, Prevention, Clinical Research, Obesity, 2.1 Biological and endogenous factors, Oral and gastrointestinal, Metabolic and endocrine, Cancer, Stroke, Adult, Animals, Body Mass Index, Drosophila, Energy Intake, Energy Metabolism, Female, Gene Frequency, Genetic Variation, Humans, Male, Proteins, Syndrome, CHD Exome+ Consortium, EPIC-CVD Consortium, ExomeBP Consortium, Global Lipids Genetic Consortium, GoT2D Genes Consortium, EPIC InterAct Consortium, INTERVAL Study, ReproGen Consortium, T2D-Genes Consortium, MAGIC Investigators, Understanding Society Scientific Group, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are ~10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed ~7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.

Published
2018

24. Meta-analysis of genome-wide association studies of HDL cholesterol response to statins

Author

Postmus, Iris, Warren, Helen R, Trompet, Stella, Arsenault, Benoit J, Avery, Christy L, Bis, Joshua C, Chasman, Daniel I, de Keyser, Catherine E, Deshmukh, Harshal A, Evans, Daniel S, Feng, QiPing, Li, Xiaohui, Smit, Roelof AJ, Smith, Albert V, Sun, Fangui, Taylor, Kent D, Arnold, Alice M, Barnes, Michael R, Barratt, Bryan J, Betteridge, John, Boekholdt, S Matthijs, Boerwinkle, Eric, Buckley, Brendan M, Chen, Y-D Ida, de Craen, Anton JM, Cummings, Steven R, Denny, Joshua C, Dubé, Marie Pierre, Durrington, Paul N, Eiriksdottir, Gudny, Ford, Ian, Guo, Xiuqing, Harris, Tamara B, Heckbert, Susan R, Hofman, Albert, Hovingh, G Kees, Kastelein, John JP, Launer, Leonore J, Liu, Ching-Ti, Liu, Yongmei, Lumley, Thomas, McKeigue, Paul M, Munroe, Patricia B, Neil, Andrew, Nickerson, Deborah A, Nyberg, Fredrik, O'Brien, Eoin, O'Donnell, Christopher J, Post, Wendy, Poulter, Neil, Vasan, Ramachandran S, Rice, Kenneth, Rich, Stephen S, Rivadeneira, Fernando, Sattar, Naveed, Sever, Peter, Shaw-Hawkins, Sue, Shields, Denis C, Slagboom, P Eline, Smith, Nicholas L, Smith, Joshua D, Sotoodehnia, Nona, Stanton, Alice, Stott, David J, Stricker, Bruno H, Stürmer, Til, Uitterlinden, André G, Wei, Wei-Qi, Westendorp, Rudi GJ, Whitsel, Eric A, Wiggins, Kerri L, Wilke, Russell A, Ballantyne, Christie M, Colhoun, Helen M, Cupples, L Adrienne, Franco, Oscar H, Gudnason, Vilmundur, Hitman, Graham, Palmer, Colin NA, Psaty, Bruce M, Ridker, Paul M, Stafford, Jeanette M, Stein, Charles M, Tardif, Jean-Claude, Caulfield, Mark J, Jukema, J Wouter, Rotter, Jerome I, and Krauss, Ronald M

Subjects
Pharmacology and Pharmaceutical Sciences, Biological Sciences, Biomedical and Clinical Sciences, Genetics, Atherosclerosis, Human Genome, Cardiovascular, Stroke, Good Health and Well Being, Cholesterol Ester Transfer Proteins, Cholesterol, HDL, Female, Genome-Wide Association Study, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Male, Pharmacogenomic Variants, Polymorphism, Single Nucleotide, Treatment Outcome, White People, Genome-wide association study, HDL-cholesterol, Statins, pharmacogenetics, Medical and Health Sciences, Genetics & Heredity, Clinical sciences
Abstract

BackgroundIn addition to lowering low density lipoprotein cholesterol (LDL-C), statin therapy also raises high density lipoprotein cholesterol (HDL-C) levels. Inter-individual variation in HDL-C response to statins may be partially explained by genetic variation.Methods and resultsWe performed a meta-analysis of genome-wide association studies (GWAS) to identify variants with an effect on statin-induced high density lipoprotein cholesterol (HDL-C) changes. The 123 most promising signals with p

Published
2016

25. Exome Genotyping Identifies Pleiotropic Variants Associated with Red Blood Cell Traits

Author

Chami, Nathalie, Chen, Ming-Huei, Slater, Andrew J, Eicher, John D, Evangelou, Evangelos, Tajuddin, Salman M, Love-Gregory, Latisha, Kacprowski, Tim, Schick, Ursula M, Nomura, Akihiro, Giri, Ayush, Lessard, Samuel, Brody, Jennifer A, Schurmann, Claudia, Pankratz, Nathan, Yanek, Lisa R, Manichaikul, Ani, Pazoki, Raha, Mihailov, Evelin, Hill, W David, Raffield, Laura M, Burt, Amber, Bartz, Traci M, Becker, Diane M, Becker, Lewis C, Boerwinkle, Eric, Bork-Jensen, Jette, Bottinger, Erwin P, O’Donoghue, Michelle L, Crosslin, David R, de Denus, Simon, Dubé, Marie-Pierre, Elliott, Paul, Engström, Gunnar, Evans, Michele K, Floyd, James S, Fornage, Myriam, Gao, He, Greinacher, Andreas, Gudnason, Vilmundur, Hansen, Torben, Harris, Tamara B, Hayward, Caroline, Hernesniemi, Jussi, Highland, Heather M, Hirschhorn, Joel N, Hofman, Albert, Irvin, Marguerite R, Kähönen, Mika, Lange, Ethan, Launer, Lenore J, Lehtimäki, Terho, Li, Jin, Liewald, David CM, Linneberg, Allan, Liu, Yongmei, Lu, Yingchang, Lyytikäinen, Leo-Pekka, Mägi, Reedik, Mathias, Rasika A, Melander, Olle, Metspalu, Andres, Mononen, Nina, Nalls, Mike A, Nickerson, Deborah A, Nikus, Kjell, O’Donnell, Chris J, Orho-Melander, Marju, Pedersen, Oluf, Petersmann, Astrid, Polfus, Linda, Psaty, Bruce M, Raitakari, Olli T, Raitoharju, Emma, Richard, Melissa, Rice, Kenneth M, Rivadeneira, Fernando, Rotter, Jerome I, Schmidt, Frank, Smith, Albert Vernon, Starr, John M, Taylor, Kent D, Teumer, Alexander, Thuesen, Betina H, Torstenson, Eric S, Tracy, Russell P, Tzoulaki, Ioanna, Zakai, Neil A, Vacchi-Suzzi, Caterina, van Duijn, Cornelia M, van Rooij, Frank JA, Cushman, Mary, Deary, Ian J, Edwards, Digna R Velez, Vergnaud, Anne-Claire, Wallentin, Lars, Waterworth, Dawn M, White, Harvey D, Wilson, James G, and Zonderman, Alan B

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Minority Health, Women's Health, Hematology, Clinical Research, Rare Diseases, Human Genome, Health Disparities, 2.1 Biological and endogenous factors, Metabolic and endocrine, Black or African American, Allelic Imbalance, Erythrocyte Indices, Erythrocytes, Erythropoiesis, Exome, Gene Frequency, Genetic Pleiotropy, Genetic Variation, Genotype, Hematocrit, Hemoglobins, Humans, Quantitative Trait Loci, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Red blood cell (RBC) traits are important heritable clinical biomarkers and modifiers of disease severity. To identify coding genetic variants associated with these traits, we conducted meta-analyses of seven RBC phenotypes in 130,273 multi-ethnic individuals from studies genotyped on an exome array. After conditional analyses and replication in 27,480 independent individuals, we identified 16 new RBC variants. We found low-frequency missense variants in MAP1A (rs55707100, minor allele frequency [MAF] = 3.3%, p = 2 × 10(-10) for hemoglobin [HGB]) and HNF4A (rs1800961, MAF = 2.4%, p < 3 × 10(-8) for hematocrit [HCT] and HGB). In African Americans, we identified a nonsense variant in CD36 associated with higher RBC distribution width (rs3211938, MAF = 8.7%, p = 7 × 10(-11)) and showed that it is associated with lower CD36 expression and strong allelic imbalance in ex vivo differentiated human erythroblasts. We also identified a rare missense variant in ALAS2 (rs201062903, MAF = 0.2%) associated with lower mean corpuscular volume and mean corpuscular hemoglobin (p < 8 × 10(-9)). Mendelian mutations in ALAS2 are a cause of sideroblastic anemia and erythropoietic protoporphyria. Gene-based testing highlighted three rare missense variants in PKLR, a gene mutated in Mendelian non-spherocytic hemolytic anemia, associated with HGB and HCT (SKAT p < 8 × 10(-7)). These rare, low-frequency, and common RBC variants showed pleiotropy, being also associated with platelet, white blood cell, and lipid traits. Our association results and functional annotation suggest the involvement of new genes in human erythropoiesis. We also confirm that rare and low-frequency variants play a role in the architecture of complex human traits, although their phenotypic effect is generally smaller than originally anticipated.

Published
2016

27. Genetics of symptom remission in outpatients with COVID-19

Author

Dubé, Marie-Pierre, Lemaçon, Audrey, Barhdadi, Amina, Lemieux Perreault, Louis-Philippe, Oussaïd, Essaïd, Asselin, Géraldine, Provost, Sylvie, Sun, Maxine, Sandoval, Johanna, Legault, Marc-André, Mongrain, Ian, Dubois, Anick, Valois, Diane, Dedelis, Emma, Lousky, Jennifer, Choi, Julie, Goulet, Elisabeth, Savard, Christiane, Chicoine, Lea-Mei, Cossette, Mariève, Chabot-Blanchet, Malorie, Guertin, Marie-Claude, de Denus, Simon, Bouabdallaoui, Nadia, Marchand, Richard, Bassevitch, Zohar, Nozza, Anna, Gaudet, Daniel, L’Allier, Philippe L., Hussin, Julie, Boivin, Guy, Busseuil, David, and Tardif, Jean-Claude

Published
2021
Full Text
View/download PDF

28. Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins.

Author

Postmus, Iris, Trompet, Stella, Deshmukh, Harshal A, Barnes, Michael R, Li, Xiaohui, Warren, Helen R, Chasman, Daniel I, Zhou, Kaixin, Arsenault, Benoit J, Donnelly, Louise A, Wiggins, Kerri L, Avery, Christy L, Griffin, Paula, Feng, QiPing, Taylor, Kent D, Li, Guo, Evans, Daniel S, Smith, Albert V, de Keyser, Catherine E, Johnson, Andrew D, de Craen, Anton JM, Stott, David J, Buckley, Brendan M, Ford, Ian, Westendorp, Rudi GJ, Slagboom, P Eline, Sattar, Naveed, Munroe, Patricia B, Sever, Peter, Poulter, Neil, Stanton, Alice, Shields, Denis C, O'Brien, Eoin, Shaw-Hawkins, Sue, Chen, Y-D Ida, Nickerson, Deborah A, Smith, Joshua D, Dubé, Marie Pierre, Boekholdt, S Matthijs, Hovingh, G Kees, Kastelein, John JP, McKeigue, Paul M, Betteridge, John, Neil, Andrew, Durrington, Paul N, Doney, Alex, Carr, Fiona, Morris, Andrew, McCarthy, Mark I, Groop, Leif, Ahlqvist, Emma, Welcome Trust Case Control Consortium, Bis, Joshua C, Rice, Kenneth, Smith, Nicholas L, Lumley, Thomas, Whitsel, Eric A, Stürmer, Til, Boerwinkle, Eric, Ngwa, Julius S, O'Donnell, Christopher J, Vasan, Ramachandran S, Wei, Wei-Qi, Wilke, Russell A, Liu, Ching-Ti, Sun, Fangui, Guo, Xiuqing, Heckbert, Susan R, Post, Wendy, Sotoodehnia, Nona, Arnold, Alice M, Stafford, Jeanette M, Ding, Jingzhong, Herrington, David M, Kritchevsky, Stephen B, Eiriksdottir, Gudny, Launer, Leonore J, Harris, Tamara B, Chu, Audrey Y, Giulianini, Franco, MacFadyen, Jean G, Barratt, Bryan J, Nyberg, Fredrik, Stricker, Bruno H, Uitterlinden, André G, Hofman, Albert, Rivadeneira, Fernando, Emilsson, Valur, Franco, Oscar H, Ridker, Paul M, Gudnason, Vilmundur, Liu, Yongmei, Denny, Joshua C, Ballantyne, Christie M, Rotter, Jerome I, Adrienne Cupples, L, Psaty, Bruce M, Palmer, Colin NA, Tardif, Jean-Claude, and Colhoun, Helen M

Subjects
Welcome Trust Case Control Consortium, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Pharmacogenetics, Polymorphism, Single Nucleotide, Cholesterol, LDL, Genome-Wide Association Study, Cholesterol, LDL, Polymorphism, Single Nucleotide
Abstract

Statins effectively lower LDL cholesterol levels in large studies and the observed interindividual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1, not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response.

Published
2014

29. A Genome-Wide Association Study of Oxypurinol Concentrations in Patients Treated with Allopurinol.

Author

Meloche, Maxime, Pilon, Marc-Olivier, Provost, Sylvie, Leclair, Grégoire, Oussaïd, Essaïd, St-Jean, Isabelle, Jutras, Martin, Gaulin, Marie-Josée, Lemieux Perreault, Louis-Philippe, Valois, Diane, Mongrain, Ian, Busseuil, David, Rouleau, Jean-Lucien, Tardif, Jean-Claude, Dubé, Marie-Pierre, and de Denus, Simon

Subjects
GENOME-wide association studies, ALLOPURINOL, DRUG metabolism
Abstract

Cohort studies have identified several genetic determinants that could predict the clinical response to allopurinol. However, they have not been commonly used for genome-wide investigations to identify genetic determinants on allopurinol metabolism and concentrations. We conducted a genome-wide association study of a prior cross-sectional investigation of patients from the Montreal Heart Institute Biobank undergoing allopurinol therapy. Four endpoints were investigated, namely plasma concentrations of oxypurinol, the active metabolite of allopurinol, allopurinol, and allopurinol-riboside, as well as allopurinol daily dosing. A total of 439 participants (mean age 69.4 years; 86.4% male) taking allopurinol (mean daily dose 194.5 mg) and who had quantifiable oxypurinol concentrations were included in the genome-wide analyses. Participants presented with multiple comorbidities and received concomitant cardiovascular medications. No association achieved the predefined genome-wide threshold values for any of the endpoints (all p > 5 × 10−8). Our results are consistent with prior findings regarding the difficulty in identifying genetic determinants of drug concentrations or pharmacokinetics of allopurinol and its metabolites, as well as allopurinol daily dosing. Given the size of this genome-wide study, collaborative investigations involving larger and diverse cohorts may be required to further identify pharmacogenomic determinants of allopurinol and measure their clinical relevance to personalize allopurinol therapy. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

31. Impact of amiodarone use on metoprolol concentrations, α‐OH‐metoprolol concentrations, metoprolol dosing and heart rate: A cross‐sectional study

Author

Robert, Sabrina, primary, Pilon, Marc‐Olivier, additional, Oussaïd, Essaïd, additional, Meloche, Maxime, additional, Leclair, Grégoire, additional, Jutras, Martin, additional, Gaulin, Marie‐Josée, additional, Mongrain, Ian, additional, Busseuil, David, additional, Tardif, Jean‐Claude, additional, Dubé, Marie‐Pierre, additional, and de Denus, Simon, additional

Published
2023
Full Text
View/download PDF

35. Platelet-Related Variants Identified by Exomechip Meta-analysis in 157,293 Individuals

Author

Eicher, John D., Chami, Nathalie, Kacprowski, Tim, Nomura, Akihiro, Chen, Ming-Huei, Yanek, Lisa R., Tajuddin, Salman M., Schick, Ursula M., Slater, Andrew J., Pankratz, Nathan, Polfus, Linda, Schurmann, Claudia, Giri, Ayush, Brody, Jennifer A., Lange, Leslie A., Manichaikul, Ani, Hill, W. David, Pazoki, Raha, Elliot, Paul, Evangelou, Evangelos, Tzoulaki, Ioanna, Gao, He, Vergnaud, Anne-Claire, Mathias, Rasika A., Becker, Diane M., Becker, Lewis C., Burt, Amber, Crosslin, David R., Lyytikäinen, Leo-Pekka, Nikus, Kjell, Hernesniemi, Jussi, Kähönen, Mika, Raitoharju, Emma, Mononen, Nina, Raitakari, Olli T., Lehtimäki, Terho, Cushman, Mary, Zakai, Neil A., Nickerson, Deborah A., Raffield, Laura M., Quarells, Rakale, Willer, Cristen J., Peloso, Gina M., Abecasis, Goncalo R., Liu, Dajiang J., Deloukas, Panos, Samani, Nilesh J., Schunkert, Heribert, Erdmann, Jeanette, Fornage, Myriam, Richard, Melissa, Tardif, Jean-Claude, Rioux, John D., Dube, Marie-Pierre, de Denus, Simon, Lu, Yingchang, Bottinger, Erwin P., Loos, Ruth J.F., Smith, Albert Vernon, Harris, Tamara B., Launer, Lenore J., Gudnason, Vilmundur, Velez Edwards, Digna R., Torstenson, Eric S., Liu, Yongmei, Tracy, Russell P., Rotter, Jerome I., Rich, Stephen S., Highland, Heather M., Boerwinkle, Eric, Li, Jin, Lange, Ethan, Wilson, James G., Mihailov, Evelin, Mägi, Reedik, Hirschhorn, Joel, Metspalu, Andres, Esko, Tõnu, Vacchi-Suzzi, Caterina, Nalls, Mike A., Zonderman, Alan B., Evans, Michele K., Engström, Gunnar, Orho-Melander, Marju, Melander, Olle, O’Donoghue, Michelle L., Waterworth, Dawn M., Wallentin, Lars, White, Harvey D., Floyd, James S., Bartz, Traci M., Rice, Kenneth M., Psaty, Bruce M., Starr, J.M., Liewald, David C.M., Hayward, Caroline, Deary, Ian J., Greinacher, Andreas, Völker, Uwe, Thiele, Thomas, Völzke, Henry, van Rooij, Frank J.A., Uitterlinden, André G., Franco, Oscar H., Dehghan, Abbas, Edwards, Todd L., Ganesh, Santhi K., Kathiresan, Sekar, Faraday, Nauder, Auer, Paul L., Reiner, Alex P., Lettre, Guillaume, and Johnson, Andrew D.

Published
2016
Full Text
View/download PDF

38. Females present higher dose‐adjusted drug concentrations of metoprolol and allopurinol/oxypurinol than males

Author

Hindi, Jessica, primary, Pilon, Marc‐Olivier, additional, Meloche, Maxime, additional, Leclair, Grégoire, additional, Oussaïd, Essaïd, additional, St‐Jean, Isabelle, additional, Jutras, Martin, additional, Gaulin, Marie‐Josée, additional, Mongrain, Ian, additional, Busseuil, David, additional, Rouleau, Jean Lucien, additional, Tardif, Jean‐Claude, additional, Dubé, Marie‐Pierre, additional, and de Denus, Simon, additional

Published
2023
Full Text
View/download PDF

39. ADCY9 (Adenylate Cyclase Type 9) Inactivation Protects From Atherosclerosis Only in the Absence of CETP (Cholesteryl Ester Transfer Protein)

Author

Rautureau, Yohann, Deschambault, Vanessa, Higgins, Marie-Ève, Rivas, Daniel, Mecteau, Mélanie, Geoffroy, Pascale, Miquel, Géraldine, Uy, Kurunradeth, Sanchez, Rocio, Lavoie, Véronique, Brand, Geneviève, Nault, Audrey, Williams, Pierre-Marc, Suarez, Maria Laura, Merlet, Nolwenn, Lapointe, Line, Duquette, Natacha, Gillis, Marc-Antoine, Samami, Samaneh, Mayer, Gaétan, Pouliot, Philippe, Raignault, Adeline, Maafi, Foued, Brodeur, Mathieu R., Levesque, Sylvie, Guertin, Marie-Claude, Dubé, Marie-Pierre, Thorin, Éric, Rhainds, David, Rhéaume, Éric, and Tardif, Jean-Claude

Published
2018
Full Text
View/download PDF

41. ABCA8 Regulates Cholesterol Efflux and High-Density Lipoprotein Cholesterol Levels

Author

Trigueros-Motos, Laia, van Capelleveen, Julian C., Torta, Federico, Castaño, David, Zhang, Lin-Hua, Chai, Ee Chu, Kang, Martin, Dimova, Lidiya G., Schimmel, Alinda W.M., Tietjen, Ian, Radomski, Chris, Tan, Liang Juin, Thiam, Chung Hwee, Narayanaswamy, Pradeep, Wu, Daniel Heqing, Dorninger, Fabian, Yakala, Gopala Krishna, Barhdadi, Amina, Angeli, Veronique, Dubé, Marie-Pierre, Berger, Johannes, Dallinga-Thie, Geesje M., Tietge, Uwe J.F., Wenk, Markus R., Hayden, Michael R., Hovingh, G. Kees, and Singaraja, Roshni R.

Published
2017
Full Text
View/download PDF

43. Somatic Mosaic Chromosomal Alterations and Death of Cardiovascular Disease Causes among Cancer Survivors.

Author

Maxine Sun, Cyr, Marie-Christyne, Sandoval, Johanna, Perreault, Louis-Philippe Lemieux, Busque, Lambert, Tardif, Jean-Claude, and Dubé, Marie-Pierre

Abstract

Background: Cancer survivors are at an increased risk of cardiovascular disease (CVD) compared with the general population. We sought to evaluate the impact of mosaic chromosomal alterations (mCA) on death of CVD causes, coronary artery disease (CAD) causes, and of any cause in patients with a cancer diagnosis. Methods: The study was a prospective cohort analysis of 48,919 UK Biobank participants with a cancer diagnosis. mCAs were characterized using DNA genotyping array intensity data and long-range chromosomal phase inference. Multivariable Cox regression models were used to ascertain the associations of mCAs. Exploratory endpoints included various incident cardiovascular phenotypes. Results: Overall, 10,070 individuals (20.6%) carried ≥ 1 mCA clone. In adjusted analyses, mCA was associated with an increased risk of death of CAD causes [HR, 1.37; 95% confidence interval (CI), 1.09-1.71; P = 0.006]. In sub-analyses, we found that carriers of mCAs diagnosed with kidney cancer had an increased risk of death of CVD causes (HR, 2.03; 95% CI, 1.11-3.72; P = 0.022) and CAD causes (HR, 3.57; 95% CI, 1.44-8.84; P = 0.006). Women diagnosed with breast cancer who carried a mCA also had a higher risk of death of CAD causes (HR, 2.46; 95% CI, 1.23-4.92; P = 0.011). Conclusions: Among cancer survivors, carriers of any mCA are at an increased risk of CAD death compared with noncarriers. Mechanistic studies should be considered to better ascertain the biological mechanisms underneath the observed associations between mCAs and cardiovascular events for specific cancer types. Impact: There may be clinical relevance in considering mCAs in patients diagnosed with cancer and undergoing treatment. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
View/download PDF

44. Pharmacogenomic study of heart failure and candesartan response from the CHARM programme

Author

Dubé, Marie‐Pierre, primary, Chazara, Olympe, additional, Lemaçon, Audrey, additional, Asselin, Géraldine, additional, Provost, Sylvie, additional, Barhdadi, Amina, additional, Lemieux Perreault, Louis‐Philippe, additional, Mongrain, Ian, additional, Wang, Quanli, additional, Carss, Keren, additional, Paul, Dirk S., additional, Cunningham, Jonathan W., additional, Rouleau, Jean, additional, Solomon, Scott D., additional, McMurray, John J.V., additional, Yusuf, Salim, additional, Granger, Chris B., additional, Haefliger, Carolina, additional, de Denus, Simon, additional, and Tardif, Jean‐Claude, additional

Published
2022
Full Text
View/download PDF

45. An association study ofABCG2rs2231142 on the concentrations of allopurinol and its metabolites

Author

Pilon, Marc‐Olivier, primary, Leclair, Grégoire, additional, Oussaïd, Essaïd, additional, St‐Jean, Isabelle, additional, Jutras, Martin, additional, Gaulin, Marie‐Josée, additional, Mongrain, Ian, additional, Busseuil, David, additional, Rouleau, Jean Lucien, additional, Tardif, Jean‐Claude, additional, Dubé, Marie‐Pierre, additional, and de Denus, Simon, additional

Published
2022
Full Text
View/download PDF

46. Mutations in DCC Cause Congenital Mirror Movements

Author

Srour, Myriam, Rivière, Jean-Baptiste, Pham, Jessica M. T., Dubé, Marie-Pierre, Girard, Simon, Morin, Steves, Dion, Patrick A., Asselin, Géraldine, Rochefort, Daniel, Hince, Pascale, Diab, Sabrina, Sharafaddinzadeh, Naser, Chouinard, Sylvain, Théoret, Hugo, Charron, Frédéric, and Rouleau, Guy A.

Published
2010

47. De novo mutations in the gene encoding the synaptic scaffolding protein SHANK3 in patients ascertained for schizophrenia

Author

Gauthier, Julie, Champagne, Nathalie, Lafrenière, Ronald G., Xiong, Lan, Spiegelman, Dan, Brustein, Edna, Lapointe, Mathieu, Peng, Huashan, Côté, Mélanie, Noreau, Anne, Hamdan, Fadi F., Addington, Anjené M., Rapoport, Judith L., DeLisi, Lynn E., Krebs, Marie-Odile, Joober, Ridha, Fathalli, Ferid, Mouaffak, Fayçal, Haghighi, Ali P., Néri, Christian, Dubé, Marie-Pierre, Samuels, Mark E., Marineau, Claude, Stone, Eric A., Awadalla, Philip, Barker, Philip A., Carbonetto, Salvatore, Drapeau, Pierre, Rouleau, Guy A., and Housman, David E.

Published
2010

48. Adenylate cyclase type 9 antagonizes cAMP accumulation and regulates endothelial signalling involved in atheroprotection

Author

Rautureau, Yohann, primary, Berlatie, Marianne, additional, Rivas, Daniel, additional, Uy, Kurunradeth, additional, Blanchette, Alexandre, additional, Miquel, Géraldine, additional, Higgins, Marie-Ève, additional, Mecteau, Mélanie, additional, Nault, Audrey, additional, Villeneuve, Louis, additional, Lavoie, Véronique, additional, Théberge-Julien, Gabriel, additional, Brand, Geneviève, additional, Lapointe, Line, additional, Denis, Maxime, additional, Rosa, Camille, additional, Fortier, Annik, additional, Blondeau, Lucie, additional, Guertin, Marie-Claude, additional, Dubé, Marie-Pierre, additional, Thorin, Éric, additional, Ledoux, Jonathan, additional, Rhainds, David, additional, Rhéaume, Éric, additional, and Tardif, Jean-Claude, additional

Published
2022
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results