The Geisinger sample collection was funded in part by the Pennsylvania Commonwealth Universal Research Enhancement program, the Geisinger Clinical Research Fund, the American Heart Association, and the Ben Franklin Technology Development Fund of Pennsylvania. Recruitment of abdominal aortic aneurysm patients and controls in Belgium, Canada, and Pittsburgh, USA, was funded in part by the National Heart, Lung, and Blood Institute, National Institutes of Health (HL064310 and HL044682). The New Zealand project was funded by the Health Research Council of New Zealand (08–75, 14–155). The Welcome Trust Case Control Consortium project was funded by the Wellcome Trust (awards 076175). This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited. Circulation Research is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. Network analyses identified ERG, IL6R, and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9.Ĭonclusions: The 4 new risk loci for AAA seem to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease.Īortic aneurysm abdominal, computational biology, genetics, genome-wide association study, matrix metalloproteinases, meta-analysis ![]() In various database searches, we observed no new associations between the lead AAA single nucleotide polymorphisms and coronary artery disease, blood pressure, lipids, or diabetes mellitus. Methods and Results: Through a meta-analysis of 6 genome-wide association study data sets and a validation study totaling 10 204 cases and 107 766 controls, we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). Objective: To identify additional AAA risk loci using data from all available genome-wide association studies. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. Rationale: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Meta-analysis of genome-wide association studies for abdominal aortic aneurysm identifies four new disease-specific risk loci.Ĭirculation Research, 120 (2). ![]() Simon, Romaine, Simon P.R., Bridge, Katherine, Griffin, Kathryn J., Bailey, Marc A., Smith, Alberto, Thompson, Matthew M., van Bockxmeer, Frank M., Matthiasson, Stefan E., Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Blankensteijn, Jan D., Teijink, Joep A.W., Wijmenga, Cisca, de Graaf, Jacqueline, Kiemeney, Lambertus A., Lindholt, Jes S., Hughes, Anne, Bradley, Declan T., Stirrups, Kathleen, Golledge, Jonathan, Norman, Paul E., Powell, Janet T., Humphries, Steve E., Hamby, Stephen E., Goodall, Alison H., Nelson, Christopher P., Sakalihasan, Natzi, Courtois, Audrey, Ferrell, Robert E., Eriksson, Per, Folkersen, Lasse, Franco-Cereceda, Anders, Eicher, John D., Johnson, Andrew D., Betsholtz, Christer, Ruusalepp, Arno, Franzén, Oscar, Schadt, Eric E., Björkegren, Johan L.M., Lipovich, Leonard, Drolet, Anne M., Verhoeven, Eric L., Zeebregts, Clark J., Geelkerken, Robert H., van Sambeek, Marc R., van Sterkenburg, Steven M., de Vries, Jean-Paul, Stefansson, Kari, Thompson, John R., de Bakker, Paul I.W., Deloukas, Panos, Sayers, Robert D., Harrison, Seamus C., van Rij, Andre M., Samani, Nilesh J., and Bown, Matthew J. Jones, Gregory T., Tromp, Gerard, Kuivaniemi, Helena, Gretarsdottir, Solveig, Baas, Annette F., Giusti, Betti, Strauss, Ewa, van'T Hof, Femke N.G., Webb, Thomas R., Erdman, Robert, Ritchie, Marylyn D., Elmore, James R., Verma, Anurag, Pendergrass, Sarah, Kullo, Iftikhar J., Ye, Zi, Peissig, Peggy L., Gottesman, Omri, Verma, Shefali S., Malinowski, Jennifer, Rasmussen-Torvik, Laura J., Borthwick, Kenneth M., Smelser, Diana T., Crosslin, David R., de Andrade, Mariza, Ryer, Evan J., McCarty, Catherine A., Böttinger, Erwin P., Pacheco, Jennifer A., Crawford, Dana C., Carrell, David S., Gerhard, Glenn S., Franklin, David P., Carey, David J., Phillips, Victoria L., Williams, Michael J.A., Wei, Wenhua, Blair, Ross, Hill, Andrew A., Vasudevan, Thodor M., Lewis, David R., Thomson, Ian A., Krysa, Jo, Hill, Geraldine B., Roake, Justin, Merriman, Tony R., Oszkinis, Grzegorz, Galora, Silvia, Saracini, Claudia, Abbate, Rosanna, Pulli, Raffaele, Pratesi, Carlo, Saratzis, Athanasios, Verissimo, Ana R., Bumpstead, Suzannah, Badger, Stephen A., Clough, Rachel E., Cockerill, Gillian, Hafez, Hany, Scott, D.
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