Large Scale Association Analysis of Novel Genetic Loci for Coronary Artery Disease.

Amouyel, P., Arveiler, D., Boekholdt, S. M., Braund, P., Bruse, P., Bumpstead, S. J., Bugert, P., Cambien, F., Danesh, J., Deloukas, P., Doering, A., Ducimetiere, P., Dunn, R. M., El Mokhtari, N. E., Erdmann, J., Evans, A., Ewels, P., Ferrieres, J., Fischer, Matthias, Frossard, P., Garner, S., Gieger, C., Gohri, M. J. R., Goodall, A. H., Grosshennig, A., Hall, A., Hardwick, R., Haukijarvi, A., Hengstenberg, C., Illig, T., Karvanen, J., Kastelein, J., Kee, F., Khaw, K. T., Kluter, H., Konig, I. R., Kuulasmaa, K., Laiho, P., Luc, G., Marz, W., McGinnis, R., McLaren, W., Meisinger, C., Morrison, C., Ou, X., Ouwehand, W. H., Preuss, M., Proust, C., Ravindrarajah, R., Renner, W., Rice, K., Ruidavets, J. B., Saleheen, D., Salomaa, V., Samani, N. J., Sandhu, M. S., Schafer, A. S., Scholz, M., Schreiber, Stefan, Schunkert, H., Silander, K., Singh, R., Soranzo, N., Stark, K., Stegmayr, B., Stephens, J., Thompson, J., Tiret, L., Trip, M. D., van der Schoot, E., Virtamo, J., Wareham, N. J., Wichmann, H. E., Wiklund, P. G., Wright, B., Ziegler, A. and Zwaginga, J. J. (2009) Large Scale Association Analysis of Novel Genetic Loci for Coronary Artery Disease. Open Access Arteriosclerosis Thrombosis and Vascular Biology, 29 (5). 774-U356. DOI 10.1161/ATVBAHA.108.181388.

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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.)

Document Type: Article
Keywords: coronary artery diseasegenetics; risk factors; genome-wide association; myocardial-infarction heart-disease; european-society; working group risk; cholesterol; population; susceptibility metaanalysis;
Research affiliation: OceanRep > The Future Ocean - Cluster of Excellence
Kiel University
OceanRep > GEOMAR > FB3 Marine Ecology > FB3-EOE-B Experimental Ecology - Benthic Ecology
Refereed: Yes
Open Access Journal?: No
DOI etc.: 10.1161/ATVBAHA.108.181388
ISSN: 1079-5642
Projects: Future Ocean
Date Deposited: 11 Feb 2011 12:15
Last Modified: 21 Jan 2019 13:00
URI: http://oceanrep.geomar.de/id/eprint/9269

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