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

Authors:
Riyaz S 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 A Kaminski Jochen D Muehlschlegel Marie-Pierre Dubé Hooman Allayee Peter Almgren Maris Alver Ekaterina V Baranova Hassan Behlouli Bram Boeckx Peter S Braund Lutz P Breitling Graciela Delgado Nubia E Duarte Line Dufresne Niclas Eriksson Luisa Foco Crystel M Gijsberts Yan Gong Jaana Hartiala Mahyar Heydarpour Jaroslav A Hubacek Marcus Kleber Daniel Kofink Pekka Kuukasjärvi Vei-Vei Lee Andreas Leiherer Petra A Lenzini Daniel Levin Leo-Pekka Lyytikäinen Nicola Martinelli Ute Mons Christopher P Nelson Kjell Nikus Anna P Pilbrow Rafal Ploski 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 R Mordi Joseph B Muhlestein Chris Newton Cheh Jan Pitha 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 G Andreassi Diego Ardissino Benoit 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 de Faire 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 P Kaczor Mika Kähönen Jiri Kettner Marek Kiliszek Olaf H Klungel Bo Lagerqvist Diether Lambrechts Jari O Laurikka Terho Lehtimäki Daniel Lindholm Bakhtawar K Mahmoodi Anke H Maitland-van der Zee Ruth McPherson Olle Melander Andres Metspalu Witold Pepinski Oliviero Olivieri Grzegorz Opolski Colin N Palmer Gerard Pasterkamp Carl J Pepine Alexandre C Pereira Louise Pilote Arshed A Quyyumi A Mark Richards Marek Sanak Markus Scholz Agneta Siegbahn Juha Sinisalo J Gustav 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 Pare 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

Circ Genom Precis Med 2019 Apr 21;12(4):e002471. Epub 2019 Mar 21.

Institute of Cardiovascular Science, Faculty of Population Health Science (R.S.P., A.F.S., L.J.H., K.D., J.D., A.D.H., F.W.A.).

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.

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCGEN.119.002471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6625876PMC
April 2019
14 Reads

Publication Analysis

Top Keywords

chromosome 9p21
16
heart disease
12
coronary heart
12
chd baseline
8
baseline genius-chd
8
established chd
8
death/myocardial infarction
8
artery disease
8
coronary artery
8
subsequent events
8
primary outcome
8
chd death/myocardial
8
odds ratio
8
subsequent coronary
8
association chromosome
8
chd
7
disease
6
subsequent
5
coronary
5
outcome data
4

References

(Supplied by CrossRef)
Subsequent event risk in individuals with established coronary heart disease: design and rationale of the GENIUS-CHD consortium.
Patel RS et al.
Circ Genom Precis Med 2019

Similar Publications