Amouyel, Philippe and Arveiler, Dominique and Boekholdt, S. Matthijs and Braund, Peter and Bruse, Petra and Bumpstead, Suzannah J. and Bugert, Peter and Cambien, Francois and Danesh, John and Deloukas, Panos and Doering, Angela and Ducimetiere, Pierre and Dunn, Ruth M. and El Mokhtari, Nour-Eddine and Erdmann, Jeanette and Evans, Alun and Ewels, Phil and Ferrieres, Jean and Fischer, Marcus and Frossard, Philippe and Garner, Stephen and Gieger, Christian and Gohri, Mohammed J. R. and Goodall, Alison H. and Grosshennig, Anika and Hall, Alistair and Hardwick, Rob and Haukijarvi, Ari and Hengstenberg, Christian and Illig, Thomas and Karvanen, Juha and Kastelein, John and Kee, Frank and Khaw, Kay-Tee and Klueter, Harald and Koenig, Inke R. and Kuulasmaa, Kari and Laiho, Paivi and Luc, Gerald and Maerz, Winfried and McGinnis, Ralph and McLaren, William and Meisinger, Christa and Morrison, Caroline and Ou, Xiodan and Ouwehand, Willem H. and Preuss, Michael and Proust, Carole and Ravindrarajah, Radhi and Renner, Wilfried and Rice, Kate and Ruidavets, Jean-Bernard and Saleheen, Danish and Salomaa, Veikko and Samani, Nilesh J. and Sandhu, Manjinder S. and Schaefer, Arne S. and Scholz, Michael and Schreiber, Stefan and Schunkert, Heribert and Silander, Kaisa and Singh, Ravi and Soranzo, Nicole and Stark, Klaus and Stegmayr, Birgitta and Stephens, Jonathan and Thompson, John and Tiret, Laurence and Trip, Mieke D. and van der Schoot, Ellen and Virtamo, Jarmo and Wareham, Nicholas J. and Wichmann, H-Erich and Wiklund, Per-Gunnar and Wright, Ben and Ziegler, Andreas and Zwaginga, Jaap-Jan (2009) Large Scale Association Analysis of Novel Genetic Loci for Coronary Artery Disease. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 29 (5). 774-U356. ISSN 1079-5642, 1524-4636
Full text not available from this repository. (Request a copy)Abstract
Background-Combined analysis of 2 genome-wide association studies in cases enriched for family history recently identified 7 loci (on 1p13.3, 1q41, 2q36.3, 6q25.1, 9p21, 10q11.21, and 15q22.33) that may affect risk of coronary artery disease (CAD). Apart from the 9p21 locus, the other loci await substantive replication. Furthermore, the effect of these loci on CAD risk in a broader range of individuals remains to be determined. Methods and Results-We undertook association analysis of single nucleotide polymorphisms at each locus with CAD risk in 11 550 cases and 11 205 controls from 9 European studies. The 9p21.3 locus showed unequivocal association (rs1333049, combined odds ratio [OR]=1.20, 95% CI [1.16 to 1.25], probability value=2.81x10(-21)). We also confirmed association signals at 1p13.3 (rs599839, OR=1.13 [1.08 to 1.19], P=1.44x10(-7)), 1q41 (rs3008621, OR=1.10 [1.04 to 1.17], P=1.02x10(-3)), and 10q11.21 (rs501120, OR=1.11 [1.05 to 1.18], P=4.34x10(-4)). The associations with 6q25.1 (rs6922269, P=0.020) and 2q36.3 (rs2943634, P=0.032) were borderline and not statistically significant after correction for multiple testing. The 15q22.33 locus did not replicate. The 10q11.21 locus showed a possible sex interaction (P = 0.015), with a significant effect in women (OR=1.29 [1.15 to 1.45], P=1.86x10(-5)) but not men (OR=1.03 [0.96 to 1.11], P=0.387). There were no other strong interactions of any of the loci with other traditional risk factors. The loci at 9p21, 1p13.3, 2q36.3, and 10q11.21 acted independently and cumulatively increased CAD risk by 15% (12% to 18%), per additional risk allele. ConclusionsThe findings provide strong evidence for association between at least 4 genetic loci and CAD risk. Cumulatively, these novel loci have a significant impact on risk of CAD at least in European populations. (Arterioscler Thromb Vasc Biol. 2009; 29: 774-780.)
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GENOME-WIDE ASSOCIATION; MYOCARDIAL-INFARCTION; HEART-DISEASE; EUROPEAN-SOCIETY; WORKING GROUP; RISK; CHOLESTEROL; POPULATION; SUSCEPTIBILITY; METAANALYSIS; coronary artery disease; genetics; risk factors |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 16 Sep 2020 05:01 |
| Last Modified: | 16 Sep 2020 05:01 |
| URI: | https://pred.uni-regensburg.de/id/eprint/28999 |
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