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1. Subsequent Event Risk in Individuals With Established Coronary Heart Disease Design and Rationale of the GENIUS-CHD Consortium

Author

Patel, Riyaz, Tragante, Vinicius, Schmidt, Amand F., McCubrey, Raymond O., Holmes, Michael V., Howe, Laurence J., Direk, Kenan, Åkerblom, Axel, Leander, Karin, Virani, Salim S., Kaminski, Karol A., Muehlschlegel, Jochen D., Allayee, Hooman, Almgren, Peter, Alver, Maris, Baranova, Ekaterina V., Behlouli, Hassan, Boeckx, Bram, Braund, Peter S., Breitling, Lutz P., Delgado, Graciela, Duarte, Nubia E., Dubé, Marie-Pierre, Dufresne, Line, Eriksson, Niclas, Foco, Luisa, Scholz, Markus, Gijsberts, Crystel M., Glinge, Charlotte, Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Hubacek, Jaroslav A., Kleber, Marcus, Kofink, Daniel, Kotti, Salma, Kuukasjärvi, Pekka, Lee, Vei-Vei, Leiherer, Andreas, Lenzini, Petra A., Levin, Daniel, Lyytikäinen, Leo-Pekka, Martinelli, Nicola, Mons, Ute, Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Ploski, Rafal, Sun, Yan V., Tanck, Michael W.T., Tang, W H Wilson, Trompet, Stella, van der Laan, Sander W., Van Setten, Jessica, Vilmundarson, Ragnar O., Viviani Anselmi, Chiara, Vlachopoulou, Efthymia, Al Ali, Lawien, Boerwinkle, Eric, Briguori, Carlo, Carlquist, John F., Carruthers, Kathryn F., Casu, Gavino, Deanfield, John, Deloukas, Panos, Dudbridge, Frank, Engström, Thomas, Fitzpatrick, Natalie, Fox, Kim, Gigante, Bruna, James, Stefan, Lokki, Marja-Liisa, Lotufo, Paulo A., Marziliano, Nicola, Mordi, Ify R., Muhlestein, Joseph B., Newton-Cheh, Christopher, Pitha, Jan, Saely, Christoph H., Samman-Tahhan, Ayman, Sandesara, Pratik B., Teren, Andrej, Timmis, Adam, Van de Werf, Frans, Wauters, Els, Wilde, Arthur A.M., Ford, Ian, Stott, David J., Algra, Ale, Andreassi, Maria G., Ardissino, Diego, Arsenault, Benoit J., Ballantyne, Christie M., Bergmeijer, Thomas O., Bezzina, Connie R., Body, Simon C., Boersma, Eric H., Bogaty, Peter, Bots, Michiel, Brenner, Hermann, Brugts, Jasper J., Burkhardt, Ralph, Carpeggiani, Clara, Condorelli, Gianluigi, Cooper-DeHoff, Rhonda M., Cresci, Sharon, Danchin, Nicolas, de Faire, Ulf, Doughty, Robert N., Drexel, Heinz, Engert, James C., Fox, Keith A.A., Girelli, Domenico, Grobbee, Diederick E., Hagström, Emil, Hazen, Stanley L., Held, Claes, Hemingway, Harry, Hoefer, Imo E., Hovingh, G. Kees, Jabbari, Reza, Johnson, Julie A., Jukema, J. Wouter, Kaczor, Marcin P., Kähönen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf H., Lagerqvist, Bo, Lambrechts, Diether, Laurikka, Jari O., Lehtimäki, Terho, Lindholm, Daniel, Mahmoodi, B.K., Maitland-van der Zee, Anke H., McPherson, Ruth, Melander, Olle, Metspalu, Andres, Niemcunowicz-Janica, Anna, Olivieri, Oliviero, Opolski, Grzegorz, Palmer, Colin N., Pasterkamp, Gerard, Pepine, Carl J., Pereira, Alexandre C., Pilote, Louise, Quyyumi, Arshed A., Richards, A. Mark, Sanak, Marek, Siegbahn, Agneta, Simon, Tabassome, Sinisalo, Juha, Smith, J. Gustav, Spertus, John A., Stender, Steen, Stewart, Alexandre F.R., Szczeklik, Wojciech, Szpakowicz, Anna, Tardif, Jean-Claude, Ten Berg, Jurriën M., Tfelt-Hansen, Jacob, Thanassoulis, George, Thiery, Joachim, Torp-Pedersen, Christian, van der Graaf, Yolanda, Visseren, Frank L.J., Waltenberger, Johannes, Weeke, Peter E., Van der Harst, Pim, Lang, Chim C., Sattar, Naveed, Cameron, Vicky A., Anderson, Jeffrey L., Brophy, James M., Paré, Guillaume, Horne, Benjamin D., März, Winfried, Wallentin, Lars, Samani, Nilesh J., Hingorani, Aroon D., Asselbergs, Folkert W., and Cardiovascular Centre (CVC)

Subjects
Adult, Male, Cardiac & Cardiovascular Systems, CARDIOVASCULAR MORTALITY, Coronary Disease, BIOBANK, Article, Sex Factors, Risk Factors, Journal Article, Humans, ARTERY-DISEASE, Cardiac and Cardiovascular Systems, genetics, Aged, Proportional Hazards Models, Genetics & Heredity, Kardiologi, Science & Technology, Smoking, Age Factors, Middle Aged, BODY-MASS INDEX, myocardial infarction, MYOCARDIAL-INFARCTION, PUBLIC-HEALTH, Cardiovascular System & Cardiology, Female, prognosis, Life Sciences & Biomedicine, coronary artery disease, secondary prevention
Abstract

BACKGROUND: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD. METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events. RESULTS: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints. CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators. ispartof: CIRCULATION-GENOMIC AND PRECISION MEDICINE vol:12 issue:4 ispartof: location:United States status: published

Published
2019
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2. Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events A GENIUS-CHD Study of Individual Participant Data

Author

Patel, Riyaz S., Schmidt, Amand F., Tragante, Vinicius, McCubrey, Raymond O., Holmes, Michael, V, Howe, Laurence J., Direk, Kenan, Åkerblom, Axel, Leander, Karin, Virani, Salim S., Kaminski, Karol A., Muehlschlegel, Jochen D., Dube, Marie-Pierre, Allayee, Hooman, Almgren, Peter, Alver, Maris, Baranova, Ekaterina, V, Behlouli, Hassan, Boeckx, Bram, Braund, Peter S., Breitling, Lutz P., Delgado, Graciela, Duarte, Nubia E., Dufresne, Line, Eriksson, Niclas, Foco, Luisa, Gijsberts, Crystel M., Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Hubacek, Jaroslav A., Kleber, Marcus, Kofink, Daniel, Kuukasjarvi, Pekka, Lee, Vei-Vei, Leiherer, Andreas, Lenzini, Petra A., Levin, Daniel, Lyytikainen, Leo-Pekka, Martinelli, Nicola, Mons, Ute, Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Ploski, Rafal, Sun, Yan, V, Tanck, Michael W. T., Tang, W. H. Wilson, Trompet, Stella, van der Laan, Sander W., van Setten, Jessica, Vilmundarson, Ragnar O., Anselmi, Chiara Viviani, Vlachopoulou, Efthymia, Boerwinkle, Eric, Briguori, Carlo, Carlquist, John F., Carruthers, Kathryn F., Casu, Gavino, Deanfield, John, Deloukas, Panos, Dudbridge, Frank, Fitzpatrick, Natalie, Gigante, Bruna, James, Stefan, Lokki, Marja-Liisa, Lotufo, Paulo A., Marziliano, Nicola, Mordi, Ify R., Muhlestein, Joseph B., Cheh, Chris Newton, Pitha, Jan, Saely, Christoph H., Samman-Tahhan, Ayman, Sandesara, Pratik B., Teren, Andrej, Timmis, Adam, Van de Werf, Frans, Wauters, Els, Wilde, Arthur A. M., Ford, Ian, Stott, David J., Algra, Ale, Andreassi, Maria G., Ardissino, Diego, Arsenault, Benoit J., Ballantyne, Christie M., Bergmeijer, Thomas O., Bezzina, Connie R., Body, Simon C., Bogaty, Peter, de Borst, Gert J., Brenner, Hermann, Burkhardt, Ralph, Carpeggiani, Clara, Condorelli, Gianluigi, Cooper-DeHoff, Rhonda M., Cresci, Sharon, de Faire, Ulf, Doughty, Robert N., Drexel, Heinz, Engert, James C., Fox, Keith A. A., Girelli, Domenico, Hagström, Emil, Hazen, Stanley L., Held, Claes, Hemingway, Harry, Hoefer, Imo E., Hovingh, G. Kees, Johnson, Julie A., De Jong, Pim A., Jukema, J. Wouter, Kaczor, Marcin P., Kahonen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf H., Lagerqvist, Bo, Lambrechts, Diether, Laurikka, Jari O., Lehtimaki, Terho, Lindholm, Daniel, Mahmoodi, Bakhtawar K., Maitland-van der Zee, Anke H., McPherson, Ruth, Melander, Olle, Metspalu, Andres, Pepinski, Witold, Olivieri, Oliviero, Opolski, Grzegorz, Palmer, Colin N., Pasterkamp, Gerard, Pepine, Carl J., Pereira, Alexandre C., Note, Louise, Quyyumi, Arshed A., Richards, A. Mark, Sanak, Marek, Scholz, Markus, Siegbahn, Agneta, Sinisalo, Juha, Smith, J. Gustav, Spertus, John A., Stewart, Alexandre F. R., Szczeklik, Wojciech, Szpakowicz, Anna, ten Berg, Jurrien M., Thanassoulis, George, Thieiy, Joachim, van der Graaf, Yolanda, Visseren, Frank L. J., Waltenberger, Johannes, Van der Harst, Pim, Tardif, Jean-Claude, Sattar, Naveed, Lang, Chim C., Pare, Guillaume, Brophy, James M., Anderson, Jeffrey L., Maerz, Winfried, Wallentin, Lars, Cameron, Vicky A., Horne, Benjamin D., Samani, Nilesh J., Hingorani, Aroon D., and Asselbergs, Folkert W.

Subjects
Genetics & Heredity, RISK, Kardiologi, Science & Technology, Cardiac & Cardiovascular Systems, VARIANTS, RECURRENT MYOCARDIAL-INFARCTION, myocardial infarction, risk factor, BIAS, Cardiovascular System & Cardiology, LOCUS, Cardiac and Cardiovascular Systems, cardiovascular diseases, chromosome, genetic, variation, Medical Genetics, Life Sciences & Biomedicine, secondary prevention, Medicinsk genetik
Abstract

BACKGROUND: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk. METHODS: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD. RESULTS: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUS-CHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction

Published
2019

3. Subsequent Event Risk in Individuals With Established Coronary Heart Disease

Author

Patel, Riyaz, Tragante, Vinicius, Schmidt, Amand, McCubrey, Raymond, Holmes, Michael, Howe, Laurence, Direk, Kenan, Åkerblom, Axel, Leander, Karin, Virani, Salim, Kaminski, Karol, Muehlschlegel, Jochen, Allayee, Hooman, Almgren, Peter, Alver, Maris, Baranova, Ekaterina, Behloui, Hassan, Boeckx, Bram, Braund, Peter, Breitling, Lutz, Delgado, Graciela, Duarte, Nubia, Dubé, Marie-Pierre, Dufresne, Line, Eriksson, Niclas, Foco, Luisa, Scholz, Markus, Gijsberts, Crystel, Glinge, Charlotte, Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Hubacek, Jaroslav, Kleber, Marcus, Kofink, Daniel, Kotti, Salma, Kuukasjärvi, Pekka, Lee, Vei-Vei, Leiherer, Andreas, Lenzini, Petra, Levin, Daniel, Lyytikäinen, Leo-Pekka, Martinelli, Nicola, Mons, Ute, Nelson, Christopher, Nikus, Kjell, Pilbrow, Anna, Ploski, Rafal, Sun, Yan, Tanck, Michael W.T., Tang, W.H.Wilson, Trompet, Stella, van der Laan, Sander, van Setten, Jessica, Vilmundarson, Ragnar, Viviani Anselmi, Chiara, Vlachopoulou, Efthymia, Al Ali, Lawien, Boerwinkle, Eric, Briguori, Carlo, Carlquist, John, Carruthers, Kathryn, Casu, Gavino, Deanfield, John, Deloukas, Panos, Dudbridge, Frank, Engstrøm, Thomas, Fitzpatrick, Natalie, Fox, Kim, Gigante, Bruna, James, Stefan, Lokki, Marja-Liisa, Lotufo, Paulo, Marziliano, Nicola, Mordi, Ify, Muhlestein, Joseph, Newton-Cheh, Christopher, Pitha, Jan, Saely, Christoph, Samman-Tahhan, Ayman, Sandesara, Pratik, Teren, Andrej, Timmis, Adam, Van De Werf, Frans, Wauters, Els, Wilde, Arthur A.M., Ford, Ian, Stott, David, Algra, Ale, Andreassi, Maria, Ardissino, Diego, Arsenault, Benoit, Ballantyne, Christie, Bergmeijer, Thomas, Bezzina, Connie, Body, Simon, Boersma, Eric, Bogaty, Peter, Bots, Michiel, Brenner, Hermann, Brugts, Jasper, Burkhardt, Ralph, Carpeggiani, Clara, Condorelli, Gianluigi, Cooper-DeHoff, Rhonda, Cresci, Sharon, Danchin, Nicolas, de Faire, Ulf, Doughty, Robert, Drexel, Heinz, Engert, James, Fox, Keith A.A., Girelli, Domenico, Grobbee, Diederick, Hagström, Emil, Hazen, Stanley, Held, Claes, Hemingway, Harry, Hoefer, Imo, Hovingh, G. Kees, Jabbari, Reza, Johnson, Julie, Jukema, J. Wouter, Kaczor, Marcin, Kähönen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf, Lagerqvist, Bo, Lambrechts, Diether, Laurikka, Jari, Lehtimäki, Terho, Lindholm, Daniel, Mahmoodi, B., Maitland-van der Zee, Anke, McPherson, Ruth, Melander, Olle, Metspalu, Andres, Niemcunowicz-Janica, Anna, Olivieri, Oliviero, Opolski, Grzegorz, Palmer, Colin, Pasterkamp, Gerard, Pepine, Carl, Pereira, Alexandre, Pilote, Louise, Quyyumi, Arshed, Richards, A. Mark, Sanak, Marek, Siegbahn, Agneta, Simon, Tabassome, Sinisalo, Juha, Smith, J. Gustav, Spertus, John, Stender, Steen, Stewart, Alexandre F.R., Szczeklik, Wojciech, Szpakowicz, Anna, Tardif, Jean-Claude, Ten Berg, Jurriën, Tfelt-Hansen, Jacob, Thanassoulis, George, Thiery, Joachim, Torp-Pedersen, Christian, Van Der Graaf, Yolanda, Visseren, Frank L.J., Waltenberger, Johannes, Weeke, Peter, van der Harst, Pim, Lang, Chim, Sattar, Naveed, Cameron, Vicky, Anderson, Jeffrey, Brophy, James, Pare, Guillaume, Horne, Benjamin, März, Winfried, Wallentin, Lars, Samani, Nilesh, Hingorani, Aroon, Asselbergs, Folkert, Centre de Ressources Biologiques APHP-SU (PASS-CRB-APHP-SU), Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Epidemiology and Data Science, APH - Methodology, Cardiology, ACS - Heart failure & arrhythmias, Vascular Medicine, ACS - Atherosclerosis & ischemic syndromes, Paediatric Pulmonology, Pulmonology, and APH - Personalized Medicine

Subjects
myocardial infarction, [SDV]Life Sciences [q-bio], genetics, prognosis, coronary artery disease, secondary prevention, ComputingMilieux_MISCELLANEOUS
Abstract

Background The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD. Methods The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events. Results Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%–100%), mostly male (44%–91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14–1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13–1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35–1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints. Conclusions GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.

Published
2019
Full Text
View/download PDF

4. Subsequent event risk in individuals with established coronary heart disease : design and rationale of the GENIUS-CHD consortium

Author

Patel, Riyaz, Tragante, Vinicius, Schmidt, Amand, McCubrey, Raymond, Holmes, Michael, Howe, Laurence, Direk, Kenan, Akerblom, Axel, Leander, Karin, Virani, Salim, Kaminski, Karol, Muehlschlegel, Jochen, Allayee, Hooman, Almgren, Peter, Alver, Maris, Baranova, Ekaterina, Behlouli, Hassan, Boeckx, Bram, Braund, Peter, Breitling, Lutz, Delgado, Graciela, Duarte, Nubia, Dube, Marie-Pierre, Dufresne, Line, Eriksson, Niclas, Foco, Luisa, Scholz, Markus, Gijsberts, Crystel, Glinge, Charlotte, Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Hubacek, Jaroslav, Kleber, Marcus, Kofink, Daniel, Kotti, Salma, Kuukasjarvi, Pekka, Lee, Vei-Vei, Leiherer, Andreas, Lenzini, Petra, Levin, Daniel, Lyytikainen, Leo-Pekka, Martinelli, Nicola, Mons, Ute, Nelson, Christopher, Nikus, Kjell, Pilbrow, Anna, Ploski, Rafal, Sun, Yan, Tanck, Michael, Tang, W.H., Trompet, Stella, van der Laan, Sander, van Setten, Jessica, Vilmundarson, Ragnar, Anselmi, Chiara, Vlachopoulou, Efthymia, Al Ali, Lawien, Boerwinkle, Eric, Briguori, Carlo, Carlquist, John, Carruthers, Kathryn, Casu, Gavino, Deanfield, John, Deloukas, Panos, Dudbridge, Frank, Engstrom, Thomas, Fitzpatrick, Natalie, Fox, Kim, Gigante, Bruna, James, Stefan, Lokki, Marja-Liisa, Lotufo, Paulo, Marziliano, Nicola, Muhlestein, Joseph, Newton-Cheh, Christopher, Pitha, Jan, Saely, Christoph, Samman-Tahhan, Ayman, Sandesara, Pratik, Teren, Andrej, Timmis, Adam, Van de Werf, Frans, Wauters, Els, Wilde, Arthur, Ford, Ian, Stott, David, Algra, Ale, Andreassi, Maria, Ardissino, Diego, Arsenault, Benoit, Ballantyne, Christie, Bergmeijer, Thomas, Bezzina, Connie, Body, Simon, Boersma, Eric, Bogaty, Peter, Bots, Michiel, Brenner, Hermann, Brugts, Jasper, Burkhardt, Ralph, Carpeggiani, Clara, Condorelli, Gianluigi, Cooper-DeHoff, Rhonda, Cresci, Sharon, Danchin, Nicolas, de Faire, Ulf, Doughty, Robert, Drexel, Heinz, Engert, James, Fox, Keith, Girelli, Domenico, Grobbee, Diederick, Hagstrom, Emil, Hazen, Stanley, Held, Claes, Hemingway, Harry, Hoefer, Imo, Hovingh, G., Jabbari, Reza, Johnson, Julie, Jukema, J., Kaczor, Marcin, Kahonen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf, Lagerqvist, Bo, Lambrechts, Diether, Laurikka, Jari, Lehtimaki, Terho, Lindholm, Daniel, Mahmoodi, B., Maitland-van der Zee, Anke, McPherson, Ruth, Melander, Olle, Metspalu, Andres, Niemcunowicz-Janica, Anna, Olivieri, Oliviero, Opolski, Grzegorz, Palmer, Colin, Pasterkamp, Gerard, Pepine, Carl, Pereira, Alexandre, Pilote, Louise, Quyyumi, Arshed, Richards, A., Sanak, Marek, Siegbahn, Agneta, Simon, Tabassome, Sinisalo, Juha, Smith, J., Spertus, John, Stender, Steen, Stewart, Alexandre, Szczeklik, Wojciech, Szpakowicz, Anna, Tardif, Jean-Claude, ten Berg, Jurrien, Tfelt-Hansen, Jacob, Thanassoulis, George, Thiery, Joachim, Torp-Pedersen, Christian, van der Graaf, Yolanda, Visseren, Frank, Waltenberger, Johannes, van der Harst, Pim, Lang, Chim, Sattar, Naveed, Cameron, Vicky, Anderson, Jeffrey, Brophy, James, Pare, Guillaume, Horne, Benjamin, Marz, Winfried, Wallentin, Lars, Samani, Nilesh, Hingorani, Aroon, and Asselbergs, Folkert

Subjects
myocardial infarction, genetics, prognosis, coronary artery disease, secondary prevention
Abstract

BACKGROUND: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD. METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events. RESULTS: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%–91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints. CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.

Published
2019

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