Association of chromosome 9p21 with subsequent coronary heart disease events: a GENUIS-CHD study of individual participant data

Patel, R. S. et al. (2019) Association of chromosome 9p21 with subsequent coronary heart disease events: a GENUIS-CHD study of individual participant data. Circulation: Genomic and Precision Medicine, 12(4), e002471. (doi: 10.1161/CIRCGEN.119.002471) (PMID:30897348)

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 <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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Stott J, Professor David and Ford, Professor Ian and Sattar, Professor Naveed
• Authors: Patel, R. S., Schmidt, A. F., Tragante, V., McCubrey, R. O., Holmes, M. V., Howe, L. J., Direk, K., Åkerblom, A., Leander, K., Virani, S. S., Kaminski, K. A., Muehlschlegel, J. D., Dubé, M.-P., Allayee, H., Almgren, P., Alver, M., Baranova, E. V., Behlouli, H., Boeckx, B., Braund, P. S., Breitling, L. P., Delgado, G., Duarte, N. E., Dufresne, L., Eriksson, N., Foco, L., Gijsberts, C. M., Gong, Y., Hartiala, J., Heydarpour, M., Hubacek, J. A., Kleber, M., Kofink, D., Kuukasjärvi, P., Lee, V.-V., Leiherer, A., Lenzini, P. A., Levin, D., Lyytikäinen, L.-P., Martinelli, N., Mons, U., Nelson, C. P., Nikus, K., Pilbrow, A. P., Ploski, R., Sun, Y. V., Tanck, M. W.T., Tang, W.H.W., Trompet, S., van der Laan, S. W., van Setten, J., Vilmundarson, R. O., Viviani Anselmi, C., Vlachopoulou, E., Boerwinkle, E., Briguori, C., Carlquist, J. F., Carruthers, K. F., Casu, G., Deanfield, J., Deloukas, P., Dudbridge, F., Fitzpatrick, N., Gigante, B., James, S., Lokki, M.-L., Lotufo, P. A., Marziliano, N., Mordi, I. R., Muhlestein, J. B., Newton Cheh, C., Pitha, J., Saely, C. H., Samman-Tahhan, A., Sandesara, P. B., Teren, A., Timmis, A., Van de Werf, F., Wauters, E., Wilde, A. A.M., Ford, I., Stott, D. J., Algra, A., Andreassi, M. G., Ardissino, D., Arsenault, B. J., Ballantyne, C. M., Bergmeijer, T. O., Bezzina, C. R., Body, S. C., Bogaty, P., de Borst, G. J., Brenner, H., Burkhardt, R., Carpeggiani, C., Condorelli, G., Cooper-DeHoff, R. M., Cresci, S., de Faire, U., Doughty, R. N., Drexel, H., Engert, J. C., Fox, K. A.A., Girelli, D., Hagström, E., Hazen, S. L., Held, C., Hemingway, H., Hoefer, I. E., Hovingh, G. K., Johnson, J. A., de Jong, P. A., Jukema, J. W., Kaczor, M. P., Kähönen, M., Kettner, J., Kiliszek, M., Klungel, O. H., Lagerqvist, B., Lambrechts, D., Laurikka, J. O., Lehtimäki, T., Lindholm, D., Mahmoodi, B. K., Maitland-van der Zee, A. H., McPherson, R., Melander, O., Metspalu, A., Pepinski, W., Olivieri, O., Opolski, G., Palmer, C. N., Pasterkamp, G., Pepine, C. J., Pereira, A. C., Pilote, L., Quyyumi, A. A., Richards, A. M., Sanak, M., Scholz, M., Siegbahn, A., Sinisalo, J., Smith, J. G., Spertus, J. A., Stewart, A. F.R., Szczeklik, W., Szpakowicz, A., ten Berg, J. M., Thanassoulis, G., Thiery, J., van der Graaf, Y., Visseren, F. L.J., Waltenberger, J., Van der Harst, P., Tardif, J.-C., Sattar, N., Lang, C. C., Pare, G., Brophy, J. M., Anderson, J. L., März, W., Wallentin, L., Cameron, V. A., Horne, B. D., Samani, N. J., Hingorani, A. D., and Asselbergs, F. W.
• Subjects: R Medicine > R Medicine (General)
• College/School: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre; College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Circulation: Genomic and Precision Medicine
• Publisher: American Heart Association
• ISSN: 2574-8300
• ISSN (Online): 2574-8300
• Published Online: 21 March 2019
• Copyright Holders: Copyright © 2019 The Authors
• First Published: First published in Circulation: Genomic and Precision Medicine 12(4): e002471
• Publisher Policy: Reproduced under a Creative Commons License