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Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events

2019; Wolters Kluwer; Volume: 12; Issue: 4 Linguagem: Inglês

10.1161/circgen.119.002471

2574-8300

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

Genomic variations and chromosomal abnormalities

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 <0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04–1.09). Conclusions: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.