Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events.
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Natalie
Fitzpatrick
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Bruna
Gigante
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Stefan
James
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Marja-Liisa
Lokki
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Paulo A
Lotufo
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Nicola
Marziliano
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Ify R
Mordi
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Joseph B
Muhlestein
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Chris
Newton Cheh
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Jan
Pitha
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Christoph H
Saely
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Ayman
Samman-Tahhan
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Pratik B
Sandesara
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Andrej
Teren
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Adam
Timmis
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Frans
Van de Werf
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Els
Wauters
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Arthur AM
Wilde
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Ian
Ford
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David J
Stott
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Ale
Algra
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Maria G
Andreassi
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Diego
Ardissino
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Benoit J
Arsenault
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Christie M
Ballantyne
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Thomas O
Bergmeijer
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Connie R
Bezzina
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Simon C
Body
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Peter
Bogaty
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Gert J
de Borst
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Hermann
Brenner
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Ralph
Burkhardt
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Clara
Carpeggiani
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Gianluigi
Condorelli
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Rhonda M
Cooper-DeHoff
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Sharon
Cresci
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Ulf
de Faire
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Robert N
Doughty
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Heinz
Drexel
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James C
Engert
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Keith AA
Fox
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Domenico
Girelli
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Emil
Hagström
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Stanley L
Hazen
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Claes
Held
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Harry
Hemingway
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Imo E
Hoefer
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G Kees
Hovingh
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Julie A
Johnson
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Pim A
de Jong
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J Wouter
Jukema
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Marcin P
Kaczor
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Mika
Kähönen
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Jiri
Kettner
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Marek
Kiliszek
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Olaf H
Klungel
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Bo
Lagerqvist
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Diether
Lambrechts
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Jari O
Laurikka
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Terho
Lehtimäki
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Daniel
Lindholm
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Bakhtawar K
Mahmoodi
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Anke H
Maitland-van der Zee
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Ruth
McPherson
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Olle
Melander
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Andres
Metspalu
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Witold
Pepinski
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Oliviero
Olivieri
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Grzegorz
Opolski
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Colin N
Palmer
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Gerard
Pasterkamp
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Carl J
Pepine
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Alexandre C
Pereira
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Louise
Pilote
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Arshed A
Quyyumi
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A Mark
Richards
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Marek
Sanak
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Markus
Scholz
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Agneta
Siegbahn
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Juha
Sinisalo
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J Gustav
Smith
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John A
Spertus
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Alexandre FR
Stewart
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Wojciech
Szczeklik
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Anna
Szpakowicz
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Jurriën M
Ten Berg
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George
Thanassoulis
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Joachim
Thiery
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Yolanda
van der Graaf
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Frank LJ
Visseren
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Johannes
Waltenberger
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CARDIoGRAMPlusC4D Consortium
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Pim
Van der Harst
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Jean-Claude
Tardif
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Naveed
Sattar
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Chim C
Lang
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Guillaume
Pare
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James M
Brophy
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Jeffrey L
Anderson
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Winfried
März
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Lars
Wallentin
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Vicky A
Cameron
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Benjamin D
Horne
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Nilesh J
Samani
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Aroon D
Hingorani
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Folkert W
Asselbergs
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(2019)
Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events.
Circulation. Genomic and precision medicine, 12 (4).
e002471-.
ISSN 2574-8300
DOI: 10.1161/CIRCGEN.119.002471
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.
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