TY - JOUR

T1 - Subsequent Event Risk in Individuals with Established Coronary Heart Disease

T2 - Design and Rationale of the GENIUS-CHD Consortium

AU - Patel, Riyaz

AU - Tragante, Vinicius

AU - Schmidt, Amand F

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 - 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 - Dubé, Marie-Pierre

AU - Dufresne, Line

AU - Eriksson, Niclas

AU - Foco, Luisa

AU - Scholz, Markus

AU - Gijsberts, Crystel M

AU - Glinge, Charlotte

AU - Gong, Yan

AU - Hartiala, Jaana

AU - Heydarpour, Mahyar

AU - Hubacek, Jaroslav A

AU - Kleber, Marcus

AU - Kofink, Daniel

AU - Kotti, Salma

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

AU - Van Setten, Jessica

AU - Vilmundarson, Ragnar O

AU - Viviani Anselmi, Chiara

AU - Vlachopoulou, Efthymia

AU - Al Ali, Lawien

AU - Boerwinkle, Eric

AU - Briguori, Carlo

AU - Carlquist, John F

AU - Carruthers, Kathryn F

AU - Casu, Gavino

AU - Deanfield, John

AU - Deloukas, Panos

AU - Dudbridge, Frank

AU - Engström, Thomas

AU - Fitzpatrick, Natalie

AU - Fox, Kim

AU - Gigante, Bruna

AU - James, Stefan

AU - Lokki, Marja-Liisa

AU - Lotufo, Paulo A

AU - Marziliano, Nicola

AU - Mordi, Ify R

AU - Muhlestein, Joseph B

AU - Newton-Cheh, Christopher

AU - Pitha, Jan

AU - Saely, Christoph H

AU - Samman-Tahhan, Ayman

AU - Sandesara, Pratik B

AU - Teren, Andrej

AU - Timmis, Adam

AU - Van de Werf, Frans

AU - Wauters, Els

AU - Wilde, Arthur A M

AU - Ford, Ian

AU - Stott, David J

AU - Algra, Ale

AU - Andreassi, Maria G

AU - Ardissino, Diego

AU - Arsenault, Benoit J

AU - Ballantyne, Christie M

AU - Bergmeijer, Thomas O

AU - Bezzina, Connie R

AU - Body, Simon C

AU - Boersma, Eric H

AU - Bogaty, Peter

AU - Bots, Michiel

AU - Brenner, Hermann

AU - Brugts, Jasper J

AU - Burkhardt, Ralph

AU - Carpeggiani, Clara

AU - Condorelli, Gianluigi

AU - Cooper-DeHoff, Rhonda M

AU - Cresci, Sharon

AU - Danchin, Nicolas

AU - de Faire, Ulf

AU - Doughty, Robert N

AU - Drexel, Heinz

AU - Engert, James C

AU - Fox, Keith A A

AU - Girelli, Domenico

AU - Grobbee, Diederick E

AU - Hagström, Emil

AU - Hazen, Stanley L

AU - Held, Claes

AU - Hemingway, Harry

AU - Hoefer, Imo E

AU - Hovingh, G Kees

AU - Jabbari, Reza

AU - Johnson, Julie A

AU - Jukema, J Wouter

AU - Kaczor, Marcin P

AU - Kähönen, Mika

AU - Kettner, Jiri

AU - Kiliszek, Marek

AU - Klungel, Olaf H

AU - Lagerqvist, Bo

AU - Lambrechts, Diether

AU - Laurikka, Jari O

AU - Lehtimäki, Terho

AU - Lindholm, Daniel

AU - Mahmoodi, B K

AU - Maitland-van der Zee, Anke H

AU - McPherson, Ruth

AU - Melander, Olle

AU - Metspalu, Andres

AU - Niemcunowicz-Janica, Anna

AU - Olivieri, Oliviero

AU - Opolski, Grzegorz

AU - Palmer, Colin N

AU - Pasterkamp, Gerard

AU - Pepine, Carl J

AU - Pereira, Alexandre C

AU - Pilote, Louise

AU - Quyyumi, Arshed A

AU - Richards, A Mark

AU - Sanak, Marek

AU - Siegbahn, Agneta

AU - Simon, Tabassome

AU - Sinisalo, Juha

AU - Smith, J Gustav

AU - Spertus, John A

AU - Stender, Steen

AU - Stewart, Alexandre F R

AU - Szczeklik, Wojciech

AU - Szpakowicz, Anna

AU - Tardif, Jean-Claude

AU - Ten Berg, Jurriën M

AU - Tfelt-Hansen, Jacob

AU - Thanassoulis, George

AU - Thiery, Joachim

AU - Torp-Pedersen, Christian

AU - van der Graaf, Yolanda

AU - Visseren, Frank L J

AU - Waltenberger, Johannes

AU - Weeke, Peter E

AU - Van der Harst, Pim

AU - Lang, Chim C

AU - Sattar, Naveed

AU - Cameron, Vicky A

AU - Anderson, Jeffrey L

AU - Brophy, James M

AU - Paré, Guillaume

AU - Horne, Benjamin D

AU - März, Winfried

AU - Wallentin, Lars

AU - Samani, Nilesh J

AU - Hingorani, Aroon D

AU - Asselbergs, Folkert W

PY - 2019/4

Y1 - 2019/4

N2 - 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.

AB - 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.

U2 - 10.1161/CIRCGEN.119.002470

DO - 10.1161/CIRCGEN.119.002470

M3 - Journal article

C2 - 30896328

VL - 12

SP - 145

EP - 160

JO - Circulation. Genomic and precision medicine

JF - Circulation. Genomic and precision medicine

SN - 2574-8300

IS - 4

M1 - e002470

ER -