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Title: Subsequent Event Risk in Individuals with Established Coronary Heart Disease: Design and Rationale of the GENIUS-CHD Consortium.
Authors: Patel, R
Tragante, V
Schmidt, AF
McCubrey, RO
Holmes, MV
Howe, LJ
Direk, K
Åkerblom, A
Leander, K
Virani, SS
Kaminski, KA
Doughty, RN
Drexel, H
Muehlschlegel, JD
Engert, JC
Fox, KAA
Girelli, D
Grobbee, DE
Hagström, E
Hazen, SL
Held, C
Breitling, LP
Hemingway, H
Hoefer, IE
Hovingh, GK
Allayee, H
Jabbari, R
Johnson, JA
Jukema, JW
Kaczor, MP
Kähönen, M
Kettner, J
Delgado, G
Kiliszek, M
Klungel, OH
Lagerqvist, B
Lambrechts, D
Almgren, P
Laurikka, JO
Lehtimäki, T
Lindholm, D
Mahmoodi, BK
Maitland-van der Zee, AH
Duarte, NE
McPherson, R
Melander, O
Metspalu, A
Niemcunowicz-Janica, A
Olivieri, O
Alver, M
Opolski, G
Palmer, CN
Pasterkamp, G
Pepine, CJ
Dubé, M-P
Pereira, AC
Pilote, L
Quyyumi, AA
Richards, AM
Sanak, M
Siegbahn, A
Baranova, EV
Simon, T
Sinisalo, J
Smith, JG
Dufresne, L
Spertus, JA
Stender, S
Stewart, AFR
Szczeklik, W
Szpakowicz, A
Tardif, J-C
Ten Berg, JM
Behlouli, H
Tfelt-Hansen, J
Thanassoulis, G
Eriksson, N
Thiery, J
Torp-Pedersen, C
van der Graaf, Y
Visseren, FLJ
Waltenberger, J
Weeke, PE
Van der Harst, P
Lang, CC
Boeckx, B
Sattar, N
Foco, L
Cameron, VA
Anderson, JL
Brophy, JM
Paré, G
Horne, BD
März, W
Wallentin, L
Samani, NJ
Hingorani, AD
Braund, PS
Scholz, M
Asselbergs, FW
Gijsberts, CM
Glinge, C
Brugts, JJ
Gong, Y
Hartiala, J
Heydarpour, M
Hubacek, JA
Kleber, M
Kofink, D
Kotti, S
Kuukasjärvi, P
Lee, V-V
Leiherer, A
Burkhardt, R
Lenzini, PA
Levin, D
Lyytikäinen, L-P
Martinelli, N
Mons, U
Nelson, CP
Nikus, K
Pilbrow, AP
Ploski, R
Sun, YV
Carpeggiani, C
Tanck, MWT
Tang, WHW
Trompet, S
van der Laan, SW
Van Setten, J
Vilmundarson, RO
Viviani Anselmi, C
Vlachopoulou, E
Al Ali, L
Boerwinkle, E
Condorelli, G
Briguori, C
Carlquist, JF
Carruthers, KF
Casu, G
Deanfield, J
Deloukas, P
Dudbridge, F
Engström, T
Fitzpatrick, N
Fox, K
Cooper-DeHoff, RM
Gigante, B
James, S
Lokki, M-L
Lotufo, PA
Marziliano, N
Mordi, IR
Muhlestein, JB
Newton-Cheh, C
Pitha, J
Saely, CH
Cresci, S
Samman-Tahhan, A
Sandesara, PB
Teren, A
Timmis, A
Van de Werf, F
Wauters, E
Wilde, AAM
Ford, I
Stott, DJ
Algra, A
Danchin, N
Andreassi, MG
Ardissino, D
Arsenault, BJ
Ballantyne, CM
Bergmeijer, TO
Bezzina, CR
Body, SC
Boersma, EH
Bogaty, P
Bots, M
de Faire, U
Brenner, H
First Published: 21-Mar-2019
Publisher: American Heart Association, Lippincott, Williams & Wilkins
Citation: Circulation: Genomic and Precision Medicine, 2019;12:e002470.
Abstract: BACKGROUND: The "GENetIcs of sUbSequent Coronary Heart Disease" (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD. METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185,614 participants with either acute coronary syndrome, stable CHD or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events. RESULTS: Enrollment into the individual studies took place between 1985 to present day with duration of follow up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (HR 1.15 95% CI 1.14-1.16) per 5-year increase, male sex (HR 1.17, 95% CI 1.13-1.21) and smoking (HR 1.43, 95% CI 1.35-1.51) with risk of subsequent CHD death or myocardial infarction, and differing associations with other individual and composite cardiovascular endpoints. CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and non-genetic determinants of subsequent event risk in individuals with established CHD, in order to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.
DOI Link: 10.1161/CIRCGEN.119.002470
eISSN: 2574-8300
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © the authors, 2019. This is an open-access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Description: The Data Supplement is available at
Appears in Collections:Published Articles, Dept. of Cardiovascular Sciences

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