Search

Your search keyword '"Kofink, Daniel"' showing total 14 results
Start Over Author "Kofink, Daniel" Database OpenAIRE
14 results on '"Kofink, Daniel"'

1. 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

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

Author

Patel, Riyaz S, 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, Behloui, 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, Klungel, Olaf H, Maitland-van der Zee, Anke H, Afd Pharmacoepi & Clinical Pharmacology, and Pharmacoepidemiology and Clinical Pharmacology

Subjects
myocardial infarction, genetics, prognosis, coronary artery disease, sedundary preventation
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

3. Association of chromosome 9p21 with subsequent coronary heart disease events: a GENUIS-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., Dubé, 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, 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, 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., Newton Cheh, Chris, 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., Kähönen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf H., Lagerqvist, Bo, Lambrechts, Diether, Laurikka, Jari O., Lehtimäki, 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., Pilote, 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, Jurriën M., Thanassoulis, George, Thiery, 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., März, Winfried, Wallentin, Lars, Cameron, Vicky A., Horne, Benjamin D., Samani, Nilesh J., Hingorani, Aroon D., and Asselbergs, Folkert W.

Subjects
cardiovascular diseases, R1
Abstract

Background:\ud 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.\ud \ud Methods:\ud 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.\ud \ud Results:\ud 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

4. 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

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

Author

Patel, Riyaz S, 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, Behloui, 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, Klungel, Olaf H, Maitland-van der Zee, Anke H, Afd Pharmacoepi & Clinical Pharmacology, and Pharmacoepidemiology and Clinical Pharmacology

Subjects
myocardial infarction, genetics, prognosis, coronary artery disease, sedundary preventation
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

6. 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

7. Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events

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, Dubé, 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, 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 WT, Tang, WH Wilson, Trompet, Stella, van der Laan, Sander W, van Setten, Jessica, Vilmundarson, Ragnar O, Viviani Anselmi, Chiara, 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, Newton Cheh, Chris, Pitha, Jan, Saely, Christoph H, Samman-Tahhan, Ayman, Sandesara, Pratik B, Teren, Andrej, Timmis, Adam, Van de Werf, Frans, Wauters, Els, Wilde, Arthur AM, 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 AA, 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, Kähönen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf H, Lagerqvist, Bo, Lambrechts, Diether, Laurikka, Jari O, Lehtimäki, 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, Pilote, Louise, Quyyumi, Arshed A, Richards, A Mark, Sanak, Marek, Scholz, Markus, Siegbahn, Agneta, Sinisalo, Juha, Smith, J Gustav, Spertus, John A, Stewart, Alexandre FR, Szczeklik, Wojciech, Szpakowicz, Anna, Ten Berg, Jurriën M, Thanassoulis, George, Thiery, Joachim, van der Graaf, Yolanda, Visseren, Frank LJ, Waltenberger, Johannes, CARDIoGRAMPlusC4D Consortium, Van der Harst, Pim, Tardif, Jean-Claude, Sattar, Naveed, Lang, Chim C, Pare, Guillaume, Brophy, James M, Anderson, Jeffrey L, März, Winfried, Wallentin, Lars, Cameron, Vicky A, Horne, Benjamin D, Samani, Nilesh J, Hingorani, Aroon D, and Asselbergs, Folkert W

Subjects
cardiovascular diseases
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

8. 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, Akerblom, 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, Tanck, Michael W.T., Wilson Tang, W.H., 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 J., 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, Hagstrom, 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, 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., Pilote, 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, Thiery, 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., Marz, Winfried, Wallentin, Lars, Cameron, Vicky A., Horne, Benjamin D., Samani, Nilesh J., Hingorani, Aroon D., and Asselbergs, Folkert W.

Published
2019

9. 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., Dubé, 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, 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, Tanck, Michael W.T., Wilde, Arthur A.M., Bezzina, Connie R., Hovingh, G. Kees, Maitland-Van der Zee, Anke H., APH - Methodology, Epidemiology and Data Science, ACS - Heart failure & arrhythmias, Cardiology, Experimental Vascular Medicine, ACS - Atherosclerosis & ischemic syndromes, Vascular Medicine, Academic Medical Center, APH - Personalized Medicine, Pulmonology, and Amsterdam Cardiovascular Sciences

Subjects
Myocardial infarction, Secondary prevention, cardiovascular diseases, Genetic variation, Risk factor, Chromosome
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 (GENIUSCHD 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

10. 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

11. Model selection for metabolomics : predicting diagnosis of coronary artery disease using automated machine learning (AutoML)

Author

Orlenko, Alena, Kofink, Daniel, Lyytikäinen, Leo-Pekka, Nikus, Kjell, Mishra, Pashupati, Kuukasjärvi, Pekka, Karhunen, Pekka, Kähönen, Mika, Laurikka, Jari, Lehtimäki, Terho, Asselberg, Folkert, Moore, Jason, Lääketieteen ja terveysteknologian tiedekunta - Faculty of Medicine and Health Technology, and Tampere University

Subjects
Sisätaudit - Internal medicine, Kirurgia, anestesiologia, tehohoito, radiologia - Surgery, anesthesiology, intensive care, radiology
Published
2019

12. Monocyte gene expression in childhood obesity is associated with obesity and complexity of atherosclerosis in adults

Author

Keustermans, G C, Kofink, Daniel, Eikendal, A.L., de Jager, W., Meerding, J., Nuboer, R., Waltenberger, J., Kraaijeveld, A.O., Jukema, J Wouter, Sels, J.W., Garssen, J, Prakken, Berent J., Asselbergs, Folkert W, Kalkhoven, E., Hoefer, Imo E., Pasterkamp, G., Schipper, Henk S, Afd Pharmacology, Pharmacology, Cardiology, Gastroenterology and Hepatology, Graduate School, General Internal Medicine, Afd Pharmacology, Pharmacology, RS: CARIM - R3 - Vascular biology, Cardiologie, Intensive Care, MUMC+: MA Med Staf Spec Cardiologie (9), and MUMC+: MA Medische Staf IC (9)

Subjects
0301 basic medicine, Male, Pediatric Obesity, PREDICTION, SUBSETS, lcsh:Medicine, Coronary Artery Disease, 030204 cardiovascular system & hematology, Coronary Angiography, Severity of Illness Index, Monocytes, Body Mass Index, Coronary artery disease, Cohort Studies, 0302 clinical medicine, IMP Dehydrogenase, Child, lcsh:Science, Foam cells, RISK, SYNTAX SCORE, Multidisciplinary, Middle Aged, medicine.anatomical_structure, METABOLIC DISEASE, Female, Adult, Adolescent, CD14, Down-Regulation, Childhood obesity, Article, 03 medical and health sciences, Monocytosis, INFLAMMATION, medicine, Humans, General, Coronary atherosclerosis, business.industry, Monocyte, lcsh:R, Case-control study, Membrane Proteins, IMMUNOMETABOLISM, medicine.disease, Atherosclerosis, Obesity, 030104 developmental biology, Case-Control Studies, Immunology, lcsh:Q, business, Transcriptome
Abstract

Childhood obesity coincides with increased numbers of circulating classical CD14++CD16- and intermediate CD14++CD16+ monocytes. Monocytes are key players in the development and exacerbation of atherosclerosis, which prompts the question as to whether the monocytosis in childhood obesity contributes to atherogenesis over the years. Here, we dissected the monocyte gene expression profile in childhood obesity using an Illumina microarray platform on sorted monocytes of 35 obese children and 16 lean controls. Obese children displayed a distinctive monocyte gene expression profile compared to lean controls. Upon validation with quantitative PCR, we studied the association of the top 5 differentially regulated monocyte genes in childhood obesity with obesity and complexity of coronary atherosclerosis (SYNTAX score) in a cohort of 351 adults at risk for ischemic cardiovascular disease. The downregulation of monocyte IMPDH2 and TMEM134 in childhood obesity was also observed in obese adults. Moreover, downregulation of monocyte TMEM134 was associated with a higher SYNTAX atherosclerosis score in adults. In conclusion, childhood obesity entails monocyte gene expression alterations associated with obesity and enhanced complexity of coronary atherosclerosis in adults.

Published
2017

13. Use of novel biomarkers to explore cardiovascular risk and drug effects

Author

Kofink, Daniel, Asselbergs, Folkert, van der Harst, P., Patel, R.S., and University Utrecht

Subjects
risk prediction, cardiovascular disease, drug effects, biomarkers, secondary prevention
Abstract

Cardiovascular disease causes immense health care costs and production losses, underscoring the need to identify individuals at risk requiring preventive treatment. This thesis aims to identify novel cardiovascular biomarkers and to advance understanding of the pathophysiological mechanisms underlying cardiovascular disease progression. Moreover, we used high-throughput metabolic profiling to study molecular drug effects. Chapter 2 relates altered monocyte gene expression in childhood obesity to atherosclerotic disease complexity in adult patients. Chapter 3 investigates the association of loss of chromosome Y with atherosclerotic plaque characteristics and clinical outcome after endarterectomy. Chapter 4 explores the ability of routinely measured hematological parameters to improve prediction of recurrent vascular events in vascular patients. The remaining chapters report results from metabolic profiling studies. Chapter 5 presents findings from a prospective study of two angiographic cohorts, in which we identified biomarkers that improve prediction of subsequent cardiovascular events. In Chapter 6, we use clinical trial data to explore the effect of metformin on metabolic profiles and to study biomarkers of infarct size and left ventricular ejection fraction after myocardial infarction. In Chapter 7, we investigate the longitudinal effect of pravastatin treatment on metabolic profiles, using data from a randomized clinical trial.

Published
2017

14. Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease : a molecular and genetic association study

Author

Zewinger, Stephen, Kleber, Marcus E., Tragante Do O, V, McCubrey, Raymond O., Schmidt, Amand F., Direk, Kenan, Laufs, Ulrich, Werner, Christian, Koenig, Wolfgang, Rothenbacher, Dietrich, Mons, Ute, Breitling, Lutz P, Brenner, Herrmann, Jennings, Richard T., Petrakis, Ioannis, Triem, Sarah, Klug, Mira, Filips, Alexandra, Blankenberg, Stefan, Waldeyer, Christoph, Sinning, Christoph, Schnabel, Renate B., Lackner, Karl J., Vlachopoulou, Efthymia, Nygård, Ottar, Svingen, Gard Frodahl Tveitevåg, Pedersen, Eva Ringdal, Tell, Grethe S., Sinisalo, Juha, Nieminen, Markku S., Laaksonen, Reijo, Trompet, Stella, Smit, Roelof A.J., Sattar, Naveed, Jukema, J. Wouter, Groesdonk, Heinrich V., Delgado, Graciela, Stojakovic, Tatjana, Pilbrow, Anna P., Cameron, Vicky A., Richards, A. Mark, Doughty, Robert N., Gong, Yan, Cooper-Dehoff, Rhonda M, Johnson, Julie A, Scholz, Markus, Kofink, Daniel, Hoefer, Imo E., Pasterkamp, Gerard, Asselbergs, Folkert W., and GENIUS-CHD consortium

Subjects
Endocrinology, Endocrinology, Diabetes and Metabolism, Internal Medicine, Journal Article
Abstract

Background Lipoprotein(a) concentrations in plasma are associated with cardiovascular risk in the general population. Whether lipoprotein(a) concentrations or LPA genetic variants predict long-term mortality in patients with established coronary heart disease remains less clear. Methods We obtained data from 3313 patients with established coronary heart disease in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We tested associations of tertiles of lipoprotein(a) concentration in plasma and two LPA single-nucleotide polymorphisms ([SNPs] rs10455872 and rs3798220) with all-cause mortality and cardiovascular mortality by Cox regression analysis and with severity of disease by generalised linear modelling, with and without adjustment for age, sex, diabetes diagnosis, systolic blood pressure, BMI, smoking status, estimated glomerular filtration rate, LDL-cholesterol concentration, and use of lipid-lowering therapy. Results for plasma lipoprotein(a) concentrations were validated in five independent studies involving 10 195 patients with established coronary heart disease. Results for genetic associations were replicated through large-scale collaborative analysis in the GENIUS-CHD consortium, comprising 106 353 patients with established coronary heart disease and 19 332 deaths in 22 studies or cohorts. Findings The median follow-up was 9·9 years. Increased severity of coronary heart disease was associated with lipoprotein(a) concentrations in plasma in the highest tertile (adjusted hazard radio [HR] 1·44, 95% CI 1·14–1·83) and the presence of either LPA SNP (1·88, 1·40–2·53). No associations were found in LURIC with all-cause mortality (highest tertile of lipoprotein(a) concentration in plasma 0·95, 0·81–1·11 and either LPA SNP 1·10, 0·92–1·31) or cardiovascular mortality (0·99, 0·81–1·2 and 1·13, 0·90–1·40, respectively) or in the validation studies. Interpretation In patients with prevalent coronary heart disease, lipoprotein(a) concentrations and genetic variants showed no associations with mortality. We conclude that these variables are not useful risk factors to measure to predict progression to death after coronary heart disease is established. Funding Seventh Framework Programme for Research and Technical Development (AtheroRemo and RiskyCAD), INTERREG IV Oberrhein Programme, Deutsche Nierenstiftung, Else-Kroener Fresenius Foundation, Deutsche Stiftung für Herzforschung, Deutsche Forschungsgemeinschaft, Saarland University, German Federal Ministry of Education and Research, Willy Robert Pitzer Foundation, and Waldburg-Zeil Clinics Isny.

Published
2017

Catalog

Books, media, physical & digital resources
See catalog results