TY - JOUR
T1 - Association of chromosome 9p21 with subsequent coronary heart disease events
T2 - A GENIUS-CHD study of individual participant data
AU - CARDIoGRAMPlusC4D Consortium
AU - Patel, Riyaz S.
AU - Schmidt, Amand F.
AU - Tragante, Vinicius
AU - McCubrey, Raymond O.
AU - Holmes, Michael V.
AU - Howe, Laurence J.
AU - Direk, Kenan
AU - Åkerblom, Axel
AU - Leander, Karin
AU - Virani, Salim S.
AU - Kaminski, Karol A.
AU - Muehlschlegel, Jochen D.
AU - Dubé, Marie Pierre
AU - Allayee, Hooman
AU - Almgren, Peter
AU - Alver, Maris
AU - Baranova, Ekaterina V.
AU - Behlouli, Hassan
AU - Boeckx, Bram
AU - Braund, Peter S.
AU - Breitling, Lutz P.
AU - Delgado, Graciela
AU - Duarte, Nubia E.
AU - Dufresne, Line
AU - Eriksson, Niclas
AU - Foco, Luisa
AU - Gijsberts, Crystel M.
AU - Gong, Yan
AU - Hartiala, Jaana
AU - Heydarpour, Mahyar
AU - Hubacek, Jaroslav A.
AU - Kleber, Marcus
AU - Kofink, Daniel
AU - Kuukasjärvi, Pekka
AU - Lee, Vei Vei
AU - Leiherer, Andreas
AU - Lenzini, Petra A.
AU - Levin, Daniel
AU - Lyytikäinen, Leo Pekka
AU - Martinelli, Nicola
AU - Mons, Ute
AU - Nelson, Christopher P.
AU - Nikus, Kjell
AU - Pilbrow, Anna P.
AU - Ploski, Rafal
AU - Sun, Yan V.
AU - Tanck, Michael W.T.
AU - Tang, W. H.Wilson
AU - Trompet, Stella
AU - Van Der Laan, Sander W.
N1 - Publisher Copyright:
© 2019 The Authors. Circulation: Genomic and Precision Medicine is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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 <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.
AB - 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 <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.
KW - Chromosome
KW - Genetic variation
KW - Myocardial infarction
KW - Risk factor
KW - Secondary prevention
UR - http://www.scopus.com/inward/record.url?scp=85071365096&partnerID=8YFLogxK
U2 - 10.1161/CIRCGEN.119.002471
DO - 10.1161/CIRCGEN.119.002471
M3 - Article
C2 - 30897348
AN - SCOPUS:85071365096
SN - 1942-325X
VL - 12
SP - 161
EP - 172
JO - Circulation. Genomic and precision medicine
JF - Circulation. Genomic and precision medicine
IS - 4
ER -