Association of Chromosome 9p21 with Subsequent Coronary Heart Disease Events: A GENIUS-CHD Study of Individual Participant Data.

Patel RS, Schmidt AF, Tragante V, McCubrey RO, Holmes MV, Howe LJ, Direk K, Åkerblom A, Leander K, Virani SS, Kaminski KA, Muehlschlegel JD, Dubé MP, Allayee H, Almgren P, Alver M, Baranova EV, Behlouli H, Boeckx B, Braund PS, Breitling LP, Delgado G, Duarte NE, Dufresne L, Eriksson N, Foco L, Gijsberts CM, Gong Y, Hartiala J, Heydarpour M, Hubacek JA, Kleber M, Kofink D, Kuukasjärvi P, Lee VV, Leiherer A, Lenzini PA, Levin D, Lyytikäinen LP, Martinelli N, Mons U, Nelson CP, Nikus K, Pilbrow AP, Ploski R, Sun YV, Tanck MWT, Tang WHW, Trompet S, van der Laan SW, Van Setten J, Vilmundarson RO, Viviani Anselmi C, Vlachopoulou E, Boerwinkle E, Briguori C, Carlquist JF, Carruthers KF, Casu G, Deanfield J, Deloukas P, Dudbridge F, Fitzpatrick N, Gigante B, James S, Lokki ML, Lotufo PA, Marziliano N, Mordi IR, Muhlestein JB, Newton-Cheh C, Pitha J, Saely CH, Samman-Tahhan A, Sandesara PB, Teren A, Timmis A, Van de Werf F, Wauters E, Wilde AAM, Ford I, Stott DJ, Algra A, Andreassi MG, Ardissino D, Arsenault BJ, Ballantyne CM, Bergmeijer TO, Bezzina CR, Body SC, Bogaty P, de Borst GJ, Brenner H, Burkhardt R, Carpeggiani C, Condorelli G, Cooper-DeHoff RM, Cresci S, de Faire U, Doughty RN, Drexel H, Engert JC, Fox KAA, Girelli D, Hagström E, Hazen SL, Held C, Hemingway H, Hoefer IE, Hovingh GK, Johnson JA, de Jong PA, Jukema JW, Kaczor MP, Kähönen M, Kettner J, Kiliszek M, Klungel OH, Lagerqvist B, Lambrechts D, Laurikka JO, Lehtimäki T, Lindholm D, Mahmoodi BK, Maitland-van der Zee AH, McPherson R, Melander O, Metspalu A, Pepinski W, Olivieri O, Opolski G, Palmer CN, Pasterkamp G, Pepine CJ, Pereira AC, Pilote L, Quyyumi AA, Richards AM, Sanak M, Scholz M, Siegbahn A, Sinisalo J, Smith JG, Spertus JA, Stewart AFR, Szczeklik W, Szpakowicz A, Ten Berg JM, Thanassoulis G, Thiery J, van der Graaf Y, Visseren FLJ, Waltenberger J, Van der Harst P, Tardif JC, Sattar N, Lang CC, Paré G, Brophy JM, Anderson JL, März W, Wallentin L, Cameron VA, Horne BD, Samani NJ, Hingorani AD, Asselbergs FW

Circ Genom Precis Med - (-) - [2019-03-21; online 2019-03-21]

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. 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 Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/MI), occurred in 13,040 of the 93,115 participants with available outcome data. Effect estimates were compared to case/control risk obtained from CARDIoGRAMPlusC4D including 47,222 CHD cases and 122,264 controls free of CHD. Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/MI among those with established CHD at baseline (GENIUS-CHD OR 1.02; 95% CI 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D OR 1.20; 95% CI 1.18-1.22; p for interaction 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.

NGI Uppsala (SNP&SEQ Technology Platform) [Service]

National Genomics Infrastructure [Service]

PubMed 30897348

DOI 10.1161/CIRCGEN.119.002471

Crossref 10.1161/CIRCGEN.119.002471