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621 results on '"Shah, Svati H."'

3. Lipoprotein subclasses are associated with Hepatic steatosis: insights from the prospective multicenter imaging study for the evaluation of chest pain (PROMISE) clinical trial

Author

Karady, Julia, McGarrah, Robert W, Nguyen, Maggie, Giamberardino, Stephanie N, Meyersohn, Nandini, Lu, Michael T, Staziaki, Pedro V, Puchner, Stefan B, Bittner, Daniel O, Foldyna, Borek, Mayrhofer, Thomas, Connelly, Margery A, Tchernof, Andre, White, Phillip J, Nasir, Khurram, Corey, Kathleen, Voora, Deepak, Pagidipati, Neha, Ginsburg, Geoffrey S, Kraus, William E, Hoffmann, Udo, Douglas, Pamela S, Shah, Svati H, and Ferencik, Maros

Published
2024
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5. Transmethylamine‐N‐Oxide Is Associated With Diffuse Cardiac Fibrosis in People Living With HIV

Author

Colaco, Nalini A, Wang, Teresa S, Ma, Yifei, Scherzer, Rebecca, Ilkayeva, Olga R, Desvigne‐Nickens, Patrice, Braunwald, Eugene, Hernandez, Adrian F, Butler, Javed, Shah, Svati H, Shah, Sanjiv J, and Hsue, Priscilla Y

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, HIV/AIDS, Biomedical Imaging, Heart Disease, Heart Disease - Coronary Heart Disease, Nutrition, Cardiovascular, Prevention, 2.1 Biological and endogenous factors, Aetiology, Good Health and Well Being, Aged, Anti-HIV Agents, Bacteria, Biomarkers, Cardiomyopathies, Cross-Sectional Studies, Female, Fibrosis, Gastrointestinal Microbiome, HIV Infections, HIV Long-Term Survivors, Humans, Male, Methylamines, Middle Aged, Myocardium, Predictive Value of Tests, Risk Assessment, Risk Factors, United States, diastolic dysfunction, HIV, myocardial fibrosis, transmethylamine-N-oxide, transmethylamine‐N‐oxide, Cardiorespiratory Medicine and Haematology, Cardiovascular medicine and haematology
Abstract

Background People living with HIV are at increased risk of developing diastolic dysfunction, heart failure, and sudden cardiac death, all of which have been characterized by higher levels of myocardial fibrosis. Transmethylamine-N-oxide (TMAO), a dietary gut metabolite, is linked to the development of myocardial fibrosis in animal models. However, it is unclear whether TMAO plays a role in the development of myocardial fibrosis in people living with HIV. Methods and Results The study population consisted of participants enrolled in the multisite cross-sectional study called CHART-HIV (Characterizing Heart Function on Anti-Retroviral Therapy). Participants underwent echocardiography, cardiac magnetic resonance imaging, biomarker analysis, and targeted assessment of gut-related circulating metabolites; diastolic dysfunction was determined by study-specific criteria. Multivariable linear regression models were performed to examine the relationship of gut-related metabolites with serum and imaging measures of myocardial fibrosis. Models were adjusted for traditional cardiovascular, inflammatory, and HIV-related risk factors. Diastolic dysfunction was present in 94 of 195 individuals (48%) in CHART-HIV; this cohort demonstrated higher prevalence of hypertension, hyperlipidemia, and chronic kidney disease as well as higher plasma levels of both TMAO and choline. TMAO levels were associated with parameters reflecting increased left ventricular filling pressures and with a marker of the innate immune system. TMAO levels correlated with diffuse myocardial fibrosis (R=0.35; P

Published
2021

6. Sequencing of 640,000 exomes identifies GPR75 variants associated with protection from obesity

Author

Akbari, Parsa, Gilani, Ankit, Sosina, Olukayode, Kosmicki, Jack A, Khrimian, Lori, Fang, Yi-Ya, Persaud, Trikaldarshi, Garcia, Victor, Sun, Dylan, Li, Alexander, Mbatchou, Joelle, Locke, Adam E, Benner, Christian, Verweij, Niek, Lin, Nan, Hossain, Sakib, Agostinucci, Kevin, Pascale, Jonathan V, Dirice, Ercument, Dunn, Michael, Center‡, Regeneron Genetics, Collaboration‡, DiscovEHR, Kraus, William E, Shah, Svati H, Chen, Yii-Der I, Rotter, Jerome I, Rader, Daniel J, Melander, Olle, Still, Christopher D, Mirshahi, Tooraj, Carey, David J, Berumen-Campos, Jaime, Kuri-Morales, Pablo, Alegre-Díaz, Jesus, Torres, Jason M, Emberson, Jonathan R, Collins, Rory, Balasubramanian, Suganthi, Hawes, Alicia, Jones, Marcus, Zambrowicz, Brian, Murphy, Andrew J, Paulding, Charles, Coppola, Giovanni, Overton, John D, Reid, Jeffrey G, Shuldiner, Alan R, Cantor, Michael, Kang, Hyun M, Abecasis, Goncalo R, Karalis, Katia, Economides, Aris N, Marchini, Jonathan, Yancopoulos, George D, Sleeman, Mark W, Altarejos, Judith, Della Gatta, Giusy, Tapia-Conyer, Roberto, Schwartzman, Michal L, Baras, Aris, Ferreira, Manuel AR, and Lotta, Luca A

Subjects
Prevention, Human Genome, Nutrition, Genetics, Obesity, Aetiology, 2.1 Biological and endogenous factors, Metabolic and endocrine, Stroke, Oral and gastrointestinal, Cardiovascular, Animals, Body Mass Index, Exome, Genetic Variation, Humans, Mice, Mice, Knockout, Receptors, G-Protein-Coupled, Sequence Analysis, DNA, Weight Gain, Regeneron Genetics Center, DiscovEHR Collaboration, General Science & Technology
Abstract

Large-scale human exome sequencing can identify rare protein-coding variants with a large impact on complex traits such as body adiposity. We sequenced the exomes of 645,626 individuals from the United Kingdom, the United States, and Mexico and estimated associations of rare coding variants with body mass index (BMI). We identified 16 genes with an exome-wide significant association with BMI, including those encoding five brain-expressed G protein-coupled receptors (CALCR, MC4R, GIPR, GPR151, and GPR75). Protein-truncating variants in GPR75 were observed in ~4/10,000 sequenced individuals and were associated with 1.8 kilograms per square meter lower BMI and 54% lower odds of obesity in the heterozygous state. Knock out of Gpr75 in mice resulted in resistance to weight gain and improved glycemic control in a high-fat diet model. Inhibition of GPR75 may provide a therapeutic strategy for obesity.

Published
2021

7. Diastolic Dysfunction in Patients With Human Immunodeficiency Virus Receiving Antiretroviral Therapy: Results From the CHART Study

Author

Butler, Javed, Greene, Stephen J, Shah, Svati H, Shah, Sanjiv J, Anstrom, Kevin J, Kim, Raymond J, Kalogeropoulos, Andreas P, Velazquez, Eric J, Hernandez, Adrian F, Desvigne-Nickens, Patrice, Scherzer, Rebecca, Hsue, Priscilla Y, and Braunwald, Eugene

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Clinical Sciences, HIV/AIDS, Cardiovascular, Infectious Diseases, Clinical Research, Heart Disease, Aetiology, 2.1 Biological and endogenous factors, Cardiomyopathies, Case-Control Studies, Cross-Sectional Studies, HIV, HIV Infections, Heart Atria, Heart Failure, Humans, Quality of Life, Ventricular Dysfunction, Left, Antiretroviral therapy, diastolic dysfunction, human immunodeficiency virus, myocardial fibrosis, Cardiorespiratory Medicine and Haematology, Nursing, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Clinical sciences
Abstract

BackgroundDiastolic dysfunction (DD) is common and occurs at an earlier age among human immunodeficiency virus-infected (HIV+) individuals, but the mechanisms and consequences of DD among HIV+ individuals are unclear.Methods and resultsThe Characterization of Heart Function on Antiretroviral Therapy (CHART) study was a multicenter cross-sectional case-control study of treated and virally suppressed HIV+ individuals with (DD+) and without DD (DD-). All patients had normal ejection fraction (>50%), no significant valvular disease, and no history of coronary revascularization or persistent atrial fibrillation. Overall, 94 DD+ and 101 DD- patients were included. DD+ patients were older with higher body mass index (BMI) and more likely to have hypertension, renal dysfunction, and dyslipidemia. Groups were similar with respect to sex, race, CD4 count, and HIV RNA copies. N-terminal pro-B-type natriuretic peptide levels (median 36 [23, 85] vs 26 [12, 49] pg/mL, P < .01) and high-sensitivity troponin I (3.6 [2.6, 5.1] vs 2.5 [1.8, 3.5] pg/mL, P < .01) were higher among DD+ patients. The latter had similar left atrial size, but increased stiffness (conduit strain: 23.5 [17.5, 36.9] vs 30.0 [22.9, 37.0], P < .01) and impaired relaxation (reservoir strain: 39.7 [32.0, 58.0] vs 45.9 [37.0, 60.6], P = .04). On cardiac magnetic resonance, the prevalence of focal fibrosis was higher among DD+ patients (19.0% vs 5.3%, P < .01). DD+ patients demonstrated higher levels of carboxyl-terminal telopeptide of collagen type I (P = .04), and trends toward higher interleukin-6 and oxidized low-density lipoprotein levels (P ≤ .08). Kansas City Cardiomyopathy Questionnaire physical limitation (87.1±21.4 vs 93.1±18.1, P = .01) and symptom frequency scores were lower among DD+ patients (86.0±21.5 vs 92.5±16.8, P = .01).ConclusionsIn this contemporary HIV+ population receiving antiretroviral therapy, DD was associated with multiple alterations in cardiac structure and function, including myocardial fibrosis and left atrial abnormalities, and worse quality of life. Further studies are needed to assess longitudinal changes in these parameters and their potential as therapeutic targets to prevent progressive cardiac remodeling and dysfunction in HIV.

Published
2020

16. Diastolic Dysfunction in Individuals With Human Immunodeficiency Virus Infection: Literature Review, Rationale and Design of the Characterizing Heart Function on Antiretroviral Therapy (CHART) Study

Author

Butler, Javed, Kalogeropoulos, Andreas P, Anstrom, Kevin J, Hsue, Priscilla Y, Kim, Raymond J, Scherzer, Rebecca, Shah, Sanjiv J, Shah, Svati H, Velazquez, Eric J, Hernandez, Adrian F, Desvigne-Nickens, Patrice, and Braunwald, Eugene

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Infectious Diseases, Cardiovascular, HIV/AIDS, Clinical Research, Heart Disease, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, 2.1 Biological and endogenous factors, Aetiology, Infection, Good Health and Well Being, Anti-Retroviral Agents, Global Health, HIV, HIV Infections, Heart Failure, Diastolic, Humans, Incidence, Prognosis, Stroke Volume, Ventricular Function, Left, Human immunodeficiency virus, diastolic dysfunction, heart failure, pathophysiology, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Nursing, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Clinical sciences
Abstract

Antiretroviral therapy (ART) has been associated with a shift in the epidemiology of human immunodeficiency virus (HIV)-associated cardiomyopathy from a phenotype of primarily left ventricular (LV) systolic dysfunction to LV diastolic dysfunction (DD). Patients with HIV receiving ART have higher rates of DD compared with age-matched control subjects and develop DD at a younger age. However, little is known about the natural history and pathogenesis of DD in virally suppressed HIV-infected patients. Current evidence suggests that immune processes modulate the risk for cardiac involvement in HIV-infected persons. Ongoing inflammation appears to have myocardial effects, and accelerated myocardial fibrosis appears to be a key mediator of HIV-induced DD. The Characterizing Heart Function on Antiretroviral Therapy (CHART) study aims to systematically investigate determinants, mechanisms, and consequences of DD in HIV-infected patients. We will compare ART-treated virally suppressed HIV-infected individuals with and without DD and HIV- individuals with DD regarding (1) systemic inflammation, myocardial stress, and subclinical myocardial necrosis as indicated by circulating biomarkers; (2) immune system activation as indicated by cell surface receptors; (3) myocardial fibrosis according to cardiac magnetic resonance examination; (4) markers of fibrosis and remodeling, oxidative stress, and hypercoagulability; (5) left atrial function according to echocardiographic examination; (6) myocardial stress and subclinical necrosis as indicated by circulating biomarkers; (7) proteomic and metabolic profiles; and (8) phenotype signatures derived from clinical, biomarker, and imaging data.

Published
2018

17. Genetic inactivation of ANGPTL4 improves glucose homeostasis and is associated with reduced risk of diabetes

Author

Gusarova, Viktoria, O’Dushlaine, Colm, Teslovich, Tanya M, Benotti, Peter N, Mirshahi, Tooraj, Gottesman, Omri, Van Hout, Cristopher V, Murray, Michael F, Mahajan, Anubha, Nielsen, Jonas B, Fritsche, Lars, Wulff, Anders Berg, Gudbjartsson, Daniel F, Sjögren, Marketa, Emdin, Connor A, Scott, Robert A, Lee, Wen-Jane, Small, Aeron, Kwee, Lydia C, Dwivedi, Om Prakash, Prasad, Rashmi B, Bruse, Shannon, Lopez, Alexander E, Penn, John, Marcketta, Anthony, Leader, Joseph B, Still, Christopher D, Kirchner, H Lester, Mirshahi, Uyenlinh L, Wardeh, Amr H, Hartle, Cassandra M, Habegger, Lukas, Fetterolf, Samantha N, Tusie-Luna, Teresa, Morris, Andrew P, Holm, Hilma, Steinthorsdottir, Valgerdur, Sulem, Patrick, Thorsteinsdottir, Unnur, Rotter, Jerome I, Chuang, Lee-Ming, Damrauer, Scott, Birtwell, David, Brummett, Chad M, Khera, Amit V, Natarajan, Pradeep, Orho-Melander, Marju, Flannick, Jason, Lotta, Luca A, Willer, Cristen J, Holmen, Oddgeir L, Ritchie, Marylyn D, Ledbetter, David H, Murphy, Andrew J, Borecki, Ingrid B, Reid, Jeffrey G, Overton, John D, Hansson, Ola, Groop, Leif, Shah, Svati H, Kraus, William E, Rader, Daniel J, Chen, Yii-Der I, Hveem, Kristian, Wareham, Nicholas J, Kathiresan, Sekar, Melander, Olle, Stefansson, Kari, Nordestgaard, Børge G, Tybjærg-Hansen, Anne, Abecasis, Goncalo R, Altshuler, David, Florez, Jose C, Boehnke, Michael, McCarthy, Mark I, Yancopoulos, George D, Carey, David J, Shuldiner, Alan R, Baras, Aris, Dewey, Frederick E, and Gromada, Jesper

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Diabetes, Atherosclerosis, Cardiovascular, Metabolic and endocrine, Amino Acid Substitution, Angiopoietin-Like Protein 4, Animals, Blood Glucose, Case-Control Studies, Diabetes Mellitus, Type 2, Female, Gene Silencing, Genetic Association Studies, Genetic Variation, Heterozygote, Homeostasis, Humans, Insulin Resistance, Lipoprotein Lipase, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Risk Factors, Exome Sequencing
Abstract

Angiopoietin-like 4 (ANGPTL4) is an endogenous inhibitor of lipoprotein lipase that modulates lipid levels, coronary atherosclerosis risk, and nutrient partitioning. We hypothesize that loss of ANGPTL4 function might improve glucose homeostasis and decrease risk of type 2 diabetes (T2D). We investigate protein-altering variants in ANGPTL4 among 58,124 participants in the DiscovEHR human genetics study, with follow-up studies in 82,766 T2D cases and 498,761 controls. Carriers of p.E40K, a variant that abolishes ANGPTL4 ability to inhibit lipoprotein lipase, have lower odds of T2D (odds ratio 0.89, 95% confidence interval 0.85-0.92, p = 6.3 × 10-10), lower fasting glucose, and greater insulin sensitivity. Predicted loss-of-function variants are associated with lower odds of T2D among 32,015 cases and 84,006 controls (odds ratio 0.71, 95% confidence interval 0.49-0.99, p = 0.041). Functional studies in Angptl4-deficient mice confirm improved insulin sensitivity and glucose homeostasis. In conclusion, genetic inactivation of ANGPTL4 is associated with improved glucose homeostasis and reduced risk of T2D.

Published
2018

20. Abstract 14174: Abnormal Exercise Electrocardiography With Normal Stress Echocardiography is Associated With Increased Subclinical Coronary Atherosclerosis: Insights From the Project Baseline Health Study

Author

Duran, Jessica M, Nguyen, Maggie, Haddad, Francois, Cauwenberghs, Nicholas, Kuznetsova, Tatiana, Bloomfield, Gerald S, Mahaffey, Kenneth, Hernandez, Adrian F, Mega, Jessica L, Short, Sarah, Douglas, Pamela S, Shah, Svati H, and Daubert, Melissa A

Published
2022
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29. Genetic and Pharmacologic Inactivation of ANGPTL3 and Cardiovascular Disease

Author

Dewey, Frederick E, Gusarova, Viktoria, Dunbar, Richard L, O'Dushlaine, Colm, Schurmann, Claudia, Gottesman, Omri, McCarthy, Shane, Van Hout, Cristopher V, Bruse, Shannon, Dansky, Hayes M, Leader, Joseph B, Murray, Michael F, Ritchie, Marylyn D, Kirchner, H Lester, Habegger, Lukas, Lopez, Alex, Penn, John, Zhao, An, Shao, Weiping, Stahl, Neil, Murphy, Andrew J, Hamon, Sara, Bouzelmat, Aurelie, Zhang, Rick, Shumel, Brad, Pordy, Robert, Gipe, Daniel, Herman, Gary A, Sheu, Wayne HH, Lee, I-Te, Liang, Kae-Woei, Guo, Xiuqing, Rotter, Jerome I, Chen, Yii-Der I, Kraus, William E, Shah, Svati H, Damrauer, Scott, Small, Aeron, Rader, Daniel J, Wulff, Anders Berg, Nordestgaard, Børge G, Tybjærg-Hansen, Anne, van den Hoek, Anita M, Princen, Hans MG, Ledbetter, David H, Carey, David J, Overton, John D, Reid, Jeffrey G, Sasiela, William J, Banerjee, Poulabi, Shuldiner, Alan R, Borecki, Ingrid B, Teslovich, Tanya M, Yancopoulos, George D, Mellis, Scott J, Gromada, Jesper, and Baras, Aris

Subjects
Genetics, Heart Disease, Clinical Research, Atherosclerosis, Heart Disease - Coronary Heart Disease, Cardiovascular, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Aged, Angiopoietin-Like Protein 3, Angiopoietin-like Proteins, Angiopoietins, Animals, Antibodies, Monoclonal, Cardiovascular Diseases, Coronary Artery Disease, Disease Models, Animal, Dose-Response Relationship, Drug, Double-Blind Method, Dyslipidemias, Female, Humans, Lipid Metabolism, Lipids, Male, Mice, Mice, Inbred Strains, Middle Aged, Mutation, Medical and Health Sciences, General & Internal Medicine
Abstract

BackgroundLoss-of-function variants in the angiopoietin-like 3 gene (ANGPTL3) have been associated with decreased plasma levels of triglycerides, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol. It is not known whether such variants or therapeutic antagonism of ANGPTL3 are associated with a reduced risk of atherosclerotic cardiovascular disease.MethodsWe sequenced the exons of ANGPTL3 in 58,335 participants in the DiscovEHR human genetics study. We performed tests of association for loss-of-function variants in ANGPTL3 with lipid levels and with coronary artery disease in 13,102 case patients and 40,430 controls from the DiscovEHR study, with follow-up studies involving 23,317 case patients and 107,166 controls from four population studies. We also tested the effects of a human monoclonal antibody, evinacumab, against Angptl3 in dyslipidemic mice and against ANGPTL3 in healthy human volunteers with elevated levels of triglycerides or LDL cholesterol.ResultsIn the DiscovEHR study, participants with heterozygous loss-of-function variants in ANGPTL3 had significantly lower serum levels of triglycerides, HDL cholesterol, and LDL cholesterol than participants without these variants. Loss-of-function variants were found in 0.33% of case patients with coronary artery disease and in 0.45% of controls (adjusted odds ratio, 0.59; 95% confidence interval, 0.41 to 0.85; P=0.004). These results were confirmed in the follow-up studies. In dyslipidemic mice, inhibition of Angptl3 with evinacumab resulted in a greater decrease in atherosclerotic lesion area and necrotic content than a control antibody. In humans, evinacumab caused a dose-dependent placebo-adjusted reduction in fasting triglyceride levels of up to 76% and LDL cholesterol levels of up to 23%.ConclusionsGenetic and therapeutic antagonism of ANGPTL3 in humans and of Angptl3 in mice was associated with decreased levels of all three major lipid fractions and decreased odds of atherosclerotic cardiovascular disease. (Funded by Regeneron Pharmaceuticals and others; ClinicalTrials.gov number, NCT01749878 .).

Published
2017

30. Potential Impact and Study Considerations of Metabolomics in Cardiovascular Health and Disease: A Scientific Statement From the American Heart Association.

Author

Cheng, Susan, Shah, Svati H, Corwin, Elizabeth J, Fiehn, Oliver, Fitzgerald, Robert L, Gerszten, Robert E, Illig, Thomas, Rhee, Eugene P, Srinivas, Pothur R, Wang, Thomas J, Jain, Mohit, American Heart Association Council on Functional Genomics and Translational Biology, Council on Cardiovascular and Stroke Nursing, Council on Clinical Cardiology, and and Stroke Council

Subjects
American Heart Association Council on Functional Genomics and Translational Biology, Council on Cardiovascular and Stroke Nursing, Council on Clinical Cardiology, and Stroke Council, Humans, Cardiovascular Diseases, American Heart Association, United States, Metabolomics, Metabolome, Microbiota, AHA Scientific Statements, cardiovascular diseases, metabolome, metabolomics, American Heart Association Council on Functional Genomics and Translational Biology, Council on Cardiovascular and Stroke Nursing, Council on Clinical Cardiology, and Stroke Council, Cardiovascular System & Hematology, Genetics, Medical Biotechnology, Cardiorespiratory Medicine and Haematology
Abstract

Through the measure of thousands of small-molecule metabolites in diverse biological systems, metabolomics now offers the potential for new insights into the factors that contribute to complex human diseases such as cardiovascular disease. Targeted metabolomics methods have already identified new molecular markers and metabolomic signatures of cardiovascular disease risk (including branched-chain amino acids, select unsaturated lipid species, and trimethylamine-N-oxide), thus in effect linking diverse exposures such as those from dietary intake and the microbiota with cardiometabolic traits. As technologies for metabolomics continue to evolve, the depth and breadth of small-molecule metabolite profiling in complex systems continue to advance rapidly, along with prospects for ongoing discovery. Current challenges facing the field of metabolomics include scaling throughput and technical capacity for metabolomics approaches, bioinformatic and chemoinformatic tools for handling large-scale metabolomics data, methods for elucidating the biochemical structure and function of novel metabolites, and strategies for determining the true clinical relevance of metabolites observed in association with cardiovascular disease outcomes. Progress made in addressing these challenges will allow metabolomics the potential to substantially affect diagnostics and therapeutics in cardiovascular medicine.

Published
2017

32. Heart Disease and Stroke Statistics—2022 Update: A Report From the American Heart Association

Author

Tsao, Connie W., Aday, Aaron W., Almarzooq, Zaid I., Alonso, Alvaro, Beaton, Andrea Z., Bittencourt, Marcio S., Boehme, Amelia K., Buxton, Alfred E., Carson, April P., Commodore-Mensah, Yvonne, Elkind, Mitchell S.V., Evenson, Kelly R., Eze-Nliam, Chete, Ferguson, Jane F., Generoso, Giuliano, Ho, Jennifer E., Kalani, Rizwan, Khan, Sadiya S., Kissela, Brett M., Knutson, Kristen L., Levine, Deborah A., Lewis, Tené T., Liu, Junxiu, Loop, Matthew Shane, Ma, Jun, Mussolino, Michael E., Navaneethan, Sankar D., Perak, Amanda Marma, Poudel, Remy, Rezk-Hanna, Mary, Roth, Gregory A., Schroeder, Emily B., Shah, Svati H., Thacker, Evan L., VanWagner, Lisa B., Virani, Salim S., Voecks, Jenifer H., Wang, Nae-Yuh, Yaffe, Kristine, and Martin, Seth S.

Published
2022
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33. Systems Genetics Analysis of Genome-Wide Association Study Reveals Novel Associations Between Key Biological Processes and Coronary Artery Disease

Author

Ghosh, Sujoy, Vivar, Juan, Nelson, Christopher P, Willenborg, Christina, Segrè, Ayellet V, Mäkinen, Ville-Petteri, Nikpay, Majid, Erdmann, Jeannette, Blankenberg, Stefan, O'Donnell, Christopher, März, Winfried, Laaksonen, Reijo, Stewart, Alexandre FR, Epstein, Stephen E, Shah, Svati H, Granger, Christopher B, Hazen, Stanley L, Kathiresan, Sekar, Reilly, Muredach P, Yang, Xia, Quertermous, Thomas, Samani, Nilesh J, Schunkert, Heribert, Assimes, Themistocles L, and McPherson, Ruth

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Heart Disease - Coronary Heart Disease, Cardiovascular, Genetics, Human Genome, Atherosclerosis, Heart Disease, Aetiology, 2.1 Biological and endogenous factors, Underpinning research, 1.1 Normal biological development and functioning, Coronary Artery Disease, Genome-Wide Association Study, Humans, coronary artery disease, pathway analysis, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Clinical sciences
Abstract

ObjectiveGenome-wide association studies have identified multiple genetic variants affecting the risk of coronary artery disease (CAD). However, individually these explain only a small fraction of the heritability of CAD and for most, the causal biological mechanisms remain unclear. We sought to obtain further insights into potential causal processes of CAD by integrating large-scale GWA data with expertly curated databases of core human pathways and functional networks.Approaches and resultsUsing pathways (gene sets) from Reactome, we carried out a 2-stage gene set enrichment analysis strategy. From a meta-analyzed discovery cohort of 7 CAD genome-wide association study data sets (9889 cases/11 089 controls), nominally significant gene sets were tested for replication in a meta-analysis of 9 additional studies (15 502 cases/55 730 controls) from the Coronary ARtery DIsease Genome wide Replication and Meta-analysis (CARDIoGRAM) Consortium. A total of 32 of 639 Reactome pathways tested showed convincing association with CAD (replication P

Published
2015

35. Association of the PHACTR1/EDN1 Genetic Locus With Spontaneous Coronary Artery Dissection

Author

Motreff, Pascal, Belle, Loïc, Dupouy, Patrick, Barnay, Pierre, Meneveau, Nicolas, Gilard, Martine, Rioufol, Gilles, Range, Grégoire, Brunel, Philippe, Delarche, Nicolas, Filippi, Emmanuelle, Le Bivic, Louis, Harbaoui, Brahim, Benamer, Hakim, Cayla, Guillaume, Varenne, Olivier, Manzo-Silberman, Stephane Peggy, Silvain, Johanne, Spaulding, Christian, Caussin, Christophe, Gerbaud, Edouard, Valy, Yann, Koning, René, Lhermusier, Thibault, Champin, Stanislas, Salengro, Emmanuel, Fluttaz, Arnaud, Zabalawi, Amer, Cottin, Yves, Teiger, Emmanuel, Saint-Etienne, Christophe, Ducrocq, Grégory, Marliere, Stéphanie, Boiffard, Emmanuel, Aubry, Pierre, Georges, Jean Louis, Bresson, Didier, De Poli, Fabien, Karrillon, Gaëtan, Roule, Vincent, Bali, Laurent, Valla, Mathieu, Gerbay, Antoine, Houpe, David, Dubreuil, Olivier, Monnier, Arsène, Mayaud, Norbert, Manchuelle, Aurélie, Commeau, Philippe, Bedossa, Marc, Nikpay, Majid, Goel, Anuj, Won, Hong-Hee, Hall, Leanne M., Willenborg, Christina, Kanoni, Stavroula, Saleheen, Danish, Kyriakou, Theodosios, Nelson, Christopher P., Hopewell, Jemma C., Webb, Thomas R., Zeng, Lingyao, Dehghan, Abbas, Alver, Maris, Armasu, Sebastian M., Auro, Kirsi, Bjonnes, Andrew, Chasman, Daniel I., Chen, Shufeng, Ford, Ian, Franceschini, Nora, Gieger, Christian, Grace, Christopher, Gustafsson, Stefan, Huang, Jie, Hwang, Shih-Jen, Kim, Yun Kyoung, Kleber, Marcus E., Lau, King Wai, Lu, Xiangfeng, Lu, Yingchang, Lyytikäinen, Leo P., Mihailov, Evelin, Morrison, Alanna, Pervjakova, Natalia, Qu, Liming, Rose, Lynda M., Salfati, Elias, Saxena, Richa, Scholz, Markus, Smith, Albert V., Tikkanen, Emmi, Uitterlinden, Andre, Yang, Xueli, Zhang, Weihua, Zhao, Wei, de Andrade, Mariza, de Vries, Paul S., van Zuydam, Natalie R., Anand, Sonia S., Bertram, Lars, Beutner, Frank, Dedoussis, George, Frossard, Philippe, Gauguier, Dominique, Goodall, Alison H., Gottesman, Omri, Haber, Marc, Han, Bok-Ghee, Huang, Jianfeng, Jalilzadeh, Shapour, Kessler, Thorsten, König, Inke R., Lannfelt, Lars, Lieb, Wolfgang, Lind, Lars, Lindgren, Cecilia M., Lokki, Maisa, Magnusson, Patrik K., Mallick, Nadeem H., Mehra, Narinder, Meitinger, Thomas, Memon, Fazal-ur-Rehman, Morris, Andrew P., Nieminen, Markku S., Pedersen, Nancy L., Peters, Annette, Rallidis, Loukianos S., Rasheed, Asif, Samuel, Maria, Shah, Svati H., Sinisalo, Juha, Stirrups, Kathleen E., Trompet, Stella, Wang, Laiyuan, Zaman, Khan S., Ardissino, Diego, Boerwinkle, Eric, Borecki, Ingrid B., Bottinger, Erwin P., Buring, Julie E., Chambers, John C., Collins, Rory, Cupples, L Adrienne, Danesh, John, Demuth, Ilja, Elosua, Roberto, Epstein, Stephen E., Esko, Tõnu, Feitosa, Mary F., Franco, Oscar H., Franzosi, Maria Grazia, Granger, Christopher B., Gu, Dongfeng, Gudnason, Vilmundur, Hall, Alistair S., Hamsten, Anders, Harris, Tamara B., Hazen, Stanley L., Hengstenberg, Christian, Hofman, Albert, Ingelsson, Erik, Iribarren, Carlos, Jukema, J Wouter, Karhunen, Pekka J., Kim, Bong-Jo, Kooner, Jaspal S., Kullo, Iftikhar J., Lehtimäki, Terho, Loos, Ruth J., Melander, Olle, Metspalu, Andres, März, Winfried, Palmer, Colin N., Perola, Markus, Quertermous, Thomas, Rader, Daniel J., Ridker, Paul M., Ripatti, Samuli, Roberts, Robert, Salomaa, Veikko, Sanghera, Dharambir K., Schwartz, Stephen M., Seedorf, Udo, Stewart, Alexandre F., Stott, David J., Thiery, Joachim, Zalloua, Pierre A., O'Donnell, Christopher J., Reilly, Muredach P., Assimes, Themistocles L., Thompson, John R., Erdmann, Jeanette, Clarke, Robert, Watkins, Hugh, Kathiresan, Sekar, McPherson, Ruth, Deloukas, Panos, Schunkert, Heribert, Samani, Nilesh J., Farrall, Martin, Adlam, David, Olson, Timothy M., Combaret, Nicolas, Kovacic, Jason C., Iismaa, Siiri E., Al-Hussaini, Abtehale, O'Byrne, Megan M., Bouajila, Sara, Georges, Adrien, Mishra, Ketan, Braund, Peter S., d’Escamard, Valentina, Huang, Siying, Margaritis, Marios, Kadian-Dodov, Daniella, Welch, Catherine A., Mazurkiewicz, Stephani, Jeunemaitre, Xavier, Wong, Claire Mei Yi, Giannoulatou, Eleni, Sweeting, Michael, Muller, David, Wood, Alice, McGrath-Cadell, Lucy, Fatkin, Diane, Dunwoodie, Sally L., Harvey, Richard, Holloway, Cameron, Empana, Jean-Philippe, Jouven, Xavier, Olin, Jeffrey W., Gulati, Rajiv, Tweet, Marysia S., Hayes, Sharonne N., Graham, Robert M., and Bouatia-Naji, Nabila

Published
2019
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38. Integrative genomics reveals novel molecular pathways and gene networks for coronary artery disease.

Author

Mäkinen, Ville-Petteri, Civelek, Mete, Meng, Qingying, Zhang, Bin, Zhu, Jun, Levian, Candace, Huan, Tianxiao, Segrè, Ayellet V, Ghosh, Sujoy, Vivar, Juan, Nikpay, Majid, Stewart, Alexandre FR, Nelson, Christopher P, Willenborg, Christina, Erdmann, Jeanette, Blakenberg, Stefan, O'Donnell, Christopher J, März, Winfried, Laaksonen, Reijo, Epstein, Stephen E, Kathiresan, Sekar, Shah, Svati H, Hazen, Stanley L, Reilly, Muredach P, Coronary ARtery DIsease Genome-Wide Replication And Meta-Analysis (CARDIoGRAM) Consortium, Lusis, Aldons J, Samani, Nilesh J, Schunkert, Heribert, Quertermous, Thomas, McPherson, Ruth, Yang, Xia, and Assimes, Themistocles L

Subjects
Coronary ARtery DIsease Genome-Wide Replication And Meta-Analysis (CARDIoGRAM) Consortium, Animals, Humans, Mice, Genetic Predisposition to Disease, Genomics, Signal Transduction, Gene Expression Regulation, Gene Regulatory Networks, Coronary Artery Disease, Genome-Wide Association Study, Developmental Biology, Genetics
Abstract

The majority of the heritability of coronary artery disease (CAD) remains unexplained, despite recent successes of genome-wide association studies (GWAS) in identifying novel susceptibility loci. Integrating functional genomic data from a variety of sources with a large-scale meta-analysis of CAD GWAS may facilitate the identification of novel biological processes and genes involved in CAD, as well as clarify the causal relationships of established processes. Towards this end, we integrated 14 GWAS from the CARDIoGRAM Consortium and two additional GWAS from the Ottawa Heart Institute (25,491 cases and 66,819 controls) with 1) genetics of gene expression studies of CAD-relevant tissues in humans, 2) metabolic and signaling pathways from public databases, and 3) data-driven, tissue-specific gene networks from a multitude of human and mouse experiments. We not only detected CAD-associated gene networks of lipid metabolism, coagulation, immunity, and additional networks with no clear functional annotation, but also revealed key driver genes for each CAD network based on the topology of the gene regulatory networks. In particular, we found a gene network involved in antigen processing to be strongly associated with CAD. The key driver genes of this network included glyoxalase I (GLO1) and peptidylprolyl isomerase I (PPIL1), which we verified as regulatory by siRNA experiments in human aortic endothelial cells. Our results suggest genetic influences on a diverse set of both known and novel biological processes that contribute to CAD risk. The key driver genes for these networks highlight potential novel targets for further mechanistic studies and therapeutic interventions.

Published
2014

39. Association of Low-Frequency and Rare Coding-Sequence Variants with Blood Lipids and Coronary Heart Disease in 56,000 Whites and Blacks

Author

Peloso, Gina M, Auer, Paul L, Bis, Joshua C, Voorman, Arend, Morrison, Alanna C, Stitziel, Nathan O, Brody, Jennifer A, Khetarpal, Sumeet A, Crosby, Jacy R, Fornage, Myriam, Isaacs, Aaron, Jakobsdottir, Johanna, Feitosa, Mary F, Davies, Gail, Huffman, Jennifer E, Manichaikul, Ani, Davis, Brian, Lohman, Kurt, Joon, Aron Y, Smith, Albert V, Grove, Megan L, Zanoni, Paolo, Redon, Valeska, Demissie, Serkalem, Lawson, Kim, Peters, Ulrike, Carlson, Christopher, Jackson, Rebecca D, Ryckman, Kelli K, Mackey, Rachel H, Robinson, Jennifer G, Siscovick, David S, Schreiner, Pamela J, Mychaleckyj, Josyf C, Pankow, James S, Hofman, Albert, Uitterlinden, Andre G, Harris, Tamara B, Taylor, Kent D, Stafford, Jeanette M, Reynolds, Lindsay M, Marioni, Riccardo E, Dehghan, Abbas, Franco, Oscar H, Patel, Aniruddh P, Lu, Yingchang, Hindy, George, Gottesman, Omri, Bottinger, Erwin P, Melander, Olle, Orho-Melander, Marju, Loos, Ruth JF, Duga, Stefano, Merlini, Piera Angelica, Farrall, Martin, Goel, Anuj, Asselta, Rosanna, Girelli, Domenico, Martinelli, Nicola, Shah, Svati H, Kraus, William E, Li, Mingyao, Rader, Daniel J, Reilly, Muredach P, McPherson, Ruth, Watkins, Hugh, Ardissino, Diego, Project, NHLBI GO Exome Sequencing, Zhang, Qunyuan, Wang, Judy, Tsai, Michael Y, Taylor, Herman A, Correa, Adolfo, Griswold, Michael E, Lange, Leslie A, Starr, John M, Rudan, Igor, Eiriksdottir, Gudny, Launer, Lenore J, Ordovas, Jose M, Levy, Daniel, Chen, Y-D Ida, Reiner, Alexander P, Hayward, Caroline, Polasek, Ozren, Deary, Ian J, Borecki, Ingrid B, Liu, Yongmei, Gudnason, Vilmundur, Wilson, James G, van Duijn, Cornelia M, Kooperberg, Charles, Rich, Stephen S, Psaty, Bruce M, Rotter, Jerome I, O’Donnell, Christopher J, Rice, Kenneth, Boerwinkle, Eric, Kathiresan, Sekar, and Cupples, L Adrienne

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Heart Disease - Coronary Heart Disease, Human Genome, Cardiovascular, Heart Disease, Atherosclerosis, Aetiology, 2.1 Biological and endogenous factors, 1-Alkyl-2-acetylglycerophosphocholine Esterase, Adult, Aged, Alleles, Animals, Black People, Cholesterol, HDL, Cholesterol, LDL, Cohort Studies, Coronary Disease, Female, Gene Frequency, Genetic Association Studies, Genetic Code, Genetic Variation, Humans, Linear Models, Male, Mice, Mice, Inbred C57BL, Microtubule-Associated Proteins, Middle Aged, Phenotype, Sequence Analysis, DNA, Subtilisins, Triglycerides, White People, NHLBI GO Exome Sequencing Project, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Low-frequency coding DNA sequence variants in the proprotein convertase subtilisin/kexin type 9 gene (PCSK9) lower plasma low-density lipoprotein cholesterol (LDL-C), protect against risk of coronary heart disease (CHD), and have prompted the development of a new class of therapeutics. It is uncertain whether the PCSK9 example represents a paradigm or an isolated exception. We used the "Exome Array" to genotype >200,000 low-frequency and rare coding sequence variants across the genome in 56,538 individuals (42,208 European ancestry [EA] and 14,330 African ancestry [AA]) and tested these variants for association with LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides. Although we did not identify new genes associated with LDL-C, we did identify four low-frequency (frequencies between 0.1% and 2%) variants (ANGPTL8 rs145464906 [c.361C>T; p.Gln121*], PAFAH1B2 rs186808413 [c.482C>T; p.Ser161Leu], COL18A1 rs114139997 [c.331G>A; p.Gly111Arg], and PCSK7 rs142953140 [c.1511G>A; p.Arg504His]) with large effects on HDL-C and/or triglycerides. None of these four variants was associated with risk for CHD, suggesting that examples of low-frequency coding variants with robust effects on both lipids and CHD will be limited.

Published
2014

40. Mitochondrial metabolites predict adverse cardiovascular events in individuals with diabetes

Author

Regan, Jessica A., primary, Mentz, Robert J., additional, Nguyen, Maggie, additional, Green, Jennifer B., additional, Truby, Lauren K., additional, Ilkayeva, Olga, additional, Newgard, Christopher B., additional, Buse, John B., additional, Sourij, Harald, additional, Sjöström, C. David, additional, Sattar, Naveed, additional, McGarrah, Robert W., additional, Zheng, Yinggan, additional, McGuire, Darren K., additional, Standl, Eberhard, additional, Armstrong, Paul, additional, Peterson, Eric D., additional, Hernandez, Adrian F., additional, Holman, Rury R., additional, and Shah, Svati H., additional

Published
2023
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41. Effect Of The Covid-19 Pandemic On Activity And Sleep In Children And Adolescents With Obesity

Author

Wagner, Brooke E., primary, Armstrong, Sarah C., additional, Skinner, Asheley, additional, Kay, Melissa C., additional, Li, Jennifer S., additional, Shah, Svati H., additional, Neshteruk, Cody D., additional, Story, Mary, additional, Suarez, Lilianna, additional, Kraus, William E., additional, Dunn, Jessilyn, additional, and Singh, Karnika, additional

Published
2023
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42. Inhaled Epoprostenol Compared With Nitric Oxide for Right Ventricular Support After Major Cardiac Surgery

Author

Ghadimi, Kamrouz, primary, Cappiello, Jhaymie L., additional, Wright, Mary Cooter, additional, Levy, Jerrold H., additional, Bryner, Benjamin S., additional, DeVore, Adam D., additional, Schroder, Jacob N., additional, Patel, Chetan B., additional, Rajagopal, Sudarshan, additional, Shah, Svati H., additional, Milano, Carmelo A., additional, Agbo, Angelito, additional, Belgique, Samuel T., additional, Bisanar, Tiffany, additional, Blank, Michael, additional, Boyle, Jason H., additional, Bottiger, Brandi A., additional, Bremenour, Carla, additional, Cherry, Anne, additional, Clark, Carl, additional, Desai, Shruti, additional, Engel, Jill, additional, Fulkerson, William J., additional, Funk, Bonita L., additional, Grecu, Loreta, additional, Hashmi, Nazish, additional, Jones, Mandisa-Maia, additional, Jones, W. Schuyler, additional, Kester, Joel, additional, Kiefer, Todd, additional, Klinger, Rebecca Y., additional, Kong, David F., additional, Krishnan, Sundar, additional, Lee, Trevor, additional, Lumbard, Jessica, additional, Maisonave, Yasmin, additional, Mamoun, Negmeldeen, additional, Manning, Michael W., additional, Mathew, Joseph P., additional, McCartney, Sharon L., additional, Moreno-Duarte, Ingrid, additional, Nicoara, Alina, additional, Owens, Thomas A., additional, Parikh, Jhana, additional, Podgoreanu, Mihai V., additional, Pollak, Angela L., additional, Ramsey, Claudette, additional, Ribet, Jacob, additional, Lorenzana, Erick, additional, Sowers, Kevin W., additional, Stafford-Smith, Mark, additional, Swaminathan, Madhav, additional, Thompson, Annemarie, additional, Van Hart, Dean, additional, Wells, Cameron, additional, Welsby, Ian J., additional, Whitacre, Meredith L., additional, and Yeboah, Vincent, additional

Published
2023
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45. Branched‐Chain Amino Acids in Computed Tomography–Defined Adipose Depots and Coronary Artery Disease: A PROMISE Trial Biomarker Substudy

Author

Zhao, Elizabeth, primary, Giamberardino, Stephanie N., additional, Pagidipati, Neha J., additional, Voora, Deepak, additional, Ginsburg, Geoffrey S., additional, Hoffmann, Udo, additional, Karády, Júlia, additional, Ferencik, Maros, additional, Douglas, Pamela S., additional, Foldyna, Borek, additional, and Shah, Svati H., additional

Published
2023
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46. Maternal Morbidity According to Mode of Delivery Among Pregnant Patients With Pulmonary Hypertension

Author

Meng, Marie-Louise, primary, Fuller, Matthew, additional, Federspiel, Jerome J., additional, Engelhard, Matthew, additional, McNeil, Ashley, additional, Ernst, Liliane, additional, Habib, Ashraf S., additional, Shah, Svati H., additional, Quist-Nelson, Johanna, additional, Raghunathan, Karthik, additional, Ohnuma, Tetsu, additional, and Krishnamoorthy, Vijay, additional

Published
2023
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47. American Heart Association's Children's Strategically Focused Research Network Experience

Author

Sable, Craig, primary, Li, Jennifer S., additional, Tristani‐Firouzi, Martin, additional, Fagerlin, Angela, additional, Silver, Robert M., additional, Yandel, Mark, additional, Yost, H. Joseph, additional, Beaton, Andrea, additional, Dale, James, additional, Engel, Mark Emmanuel, additional, Watkins, David, additional, Spurney, Christopher, additional, Skinner, Asheley C., additional, Armstrong, Sarah C., additional, Shah, Svati H., additional, Allen, Norrina, additional, Davis, Matthew, additional, Hou, Lifang, additional, Van Horn, Linda, additional, Labarthe, Darwin, additional, Lloyd‐Jones, Donald, additional, and Marino, Bradley, additional

Published
2023
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