Szilard Voros1, Pal Maurovich-Horvat2, Idean B Marvasty3, Aruna T Bansal4, Michael R Barnes5, Gustavo Vazquez6, Sarah S Murray7, Viktor Voros3, Bela Merkely2, Bradley O Brown3, G Russell Warnick8. 1. Global Genomics Group, LLC, 737 N. 5th Street, Richmond, VA 23219, USA. Electronic address: szilardvorosmd@gmail.com. 2. Semmelweis University, Budapest, Hungary. 3. Global Genomics Group, LLC, 737 N. 5th Street, Richmond, VA 23219, USA. 4. Acclarogen, Ltd. Cambridge, UK. 5. Queen Mary University, London, UK. 6. Global Institute for Research, LLC, Richmond, VA, USA. 7. University of California at San Diego, San Diego, CA, USA. 8. Health Diagnostic Laboratory, LLC, Richmond, VA, USA.
Abstract
BACKGROUND: Complex biological networks of atherosclerosis are largely unknown. OBJECTIVE: The main objective of the Genetic Loci and the Burden of Atherosclerotic Lesions study is to assemble comprehensive biological networks of atherosclerosis using advanced cardiovascular imaging for phenotyping, a panomic approach to identify underlying genomic, proteomic, metabolomic, and lipidomic underpinnings, analyzed by systems biology-driven bioinformatics. METHODS: By design, this is a hypothesis-free unbiased discovery study collecting a large number of biologically related factors to examine biological associations between genomic, proteomic, metabolomic, lipidomic, and phenotypic factors of atherosclerosis. The Genetic Loci and the Burden of Atherosclerotic Lesions study (NCT01738828) is a prospective, multicenter, international observational study of atherosclerotic coronary artery disease. Approximately 7500 patients are enrolled and undergo non-contrast-enhanced coronary calcium scanning by CT for the detection and quantification of coronary artery calcium, as well as coronary artery CT angiography for the detection and quantification of plaque, stenosis, and overall coronary artery disease burden. In addition, patients undergo whole genome sequencing, DNA methylation, whole blood-based transcriptome sequencing, unbiased proteomics based on mass spectrometry, as well as metabolomics and lipidomics on a mass spectrometry platform. The study is analyzed in 3 subsequent phases, and each phase consists of a discovery cohort and an independent validation cohort. For the primary analysis, the primary phenotype will be the presence of any atherosclerotic plaque, as detected by cardiac CT. Additional phenotypic analyses will include per patient maximal luminal stenosis defined as 50% and 70% diameter stenosis. Single-omic and multi-omic associations will be examined for each phenotype; putative biomarkers will be assessed for association, calibration, discrimination, and reclassification.
BACKGROUND: Complex biological networks of atherosclerosis are largely unknown. OBJECTIVE: The main objective of the Genetic Loci and the Burden of Atherosclerotic Lesions study is to assemble comprehensive biological networks of atherosclerosis using advanced cardiovascular imaging for phenotyping, a panomic approach to identify underlying genomic, proteomic, metabolomic, and lipidomic underpinnings, analyzed by systems biology-driven bioinformatics. METHODS: By design, this is a hypothesis-free unbiased discovery study collecting a large number of biologically related factors to examine biological associations between genomic, proteomic, metabolomic, lipidomic, and phenotypic factors of atherosclerosis. The Genetic Loci and the Burden of Atherosclerotic Lesions study (NCT01738828) is a prospective, multicenter, international observational study of atherosclerotic coronary artery disease. Approximately 7500 patients are enrolled and undergo non-contrast-enhanced coronary calcium scanning by CT for the detection and quantification of coronary artery calcium, as well as coronary artery CT angiography for the detection and quantification of plaque, stenosis, and overall coronary artery disease burden. In addition, patients undergo whole genome sequencing, DNA methylation, whole blood-based transcriptome sequencing, unbiased proteomics based on mass spectrometry, as well as metabolomics and lipidomics on a mass spectrometry platform. The study is analyzed in 3 subsequent phases, and each phase consists of a discovery cohort and an independent validation cohort. For the primary analysis, the primary phenotype will be the presence of any atherosclerotic plaque, as detected by cardiac CT. Additional phenotypic analyses will include per patient maximal luminal stenosis defined as 50% and 70% diameter stenosis. Single-omic and multi-omic associations will be examined for each phenotype; putative biomarkers will be assessed for association, calibration, discrimination, and reclassification.
Authors: A L Jermendy; M Kolossvary; Z D Drobni; A D Tarnoki; D L Tarnoki; J Karady; S Voros; H J Lamb; B Merkely; G Jermendy; P Maurovich-Horvat Journal: Int J Obes (Lond) Date: 2017-08-30 Impact factor: 5.095
Authors: Thiago Morelli; Kevin L Moss; John S Preisser; James D Beck; Kimon Divaris; Di Wu; Steven Offenbacher Journal: J Periodontol Date: 2018-02-22 Impact factor: 6.993
Authors: Pál Maurovich-Horvat; Dávid L Tárnoki; Ádám D Tárnoki; Tamás Horváth; Ádám L Jermendy; Márton Kolossváry; Bálint Szilveszter; Viktor Voros; Attila Kovács; Andrea Á Molnár; Levente Littvay; Hildo J Lamb; Szilard Voros; György Jermendy; Béla Merkely Journal: Clin Cardiol Date: 2015-10-23 Impact factor: 2.882
Authors: Tudor Groza; Sebastian Köhler; Dawid Moldenhauer; Nicole Vasilevsky; Gareth Baynam; Tomasz Zemojtel; Lynn Marie Schriml; Warren Alden Kibbe; Paul N Schofield; Tim Beck; Drashtti Vasant; Anthony J Brookes; Andreas Zankl; Nicole L Washington; Christopher J Mungall; Suzanna E Lewis; Melissa A Haendel; Helen Parkinson; Peter N Robinson Journal: Am J Hum Genet Date: 2015-06-25 Impact factor: 11.025
Authors: John Whitaker; Júlia Karády; Rashed Karim; Catalina Tobon-Gomez; Thomas Fastl; Orod Razeghi; Louisa O'Neill; Marie Decroocq; Steven Williams; Cesare Corrado; Rahul K Mukherjee; Iain Sim; Daniel O'Hare; Irum Kotadia; Márton Kolossváry; Bela Merkely; Levente Littvay; Adam D Tarnoki; David L Tarnoki; Szilard Voros; Reza Razavi; Mark O'Neill; Ronak Rajani; Pál Maurovich Horvat; Steven Niederer Journal: Int J Cardiol Heart Vasc Date: 2020-12-24