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Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci

Jones, Gregory T. (author)
Tromp, Gerard (author)
Kuivaniemi, Helena (author)
show more...
Gretarsdottir, Solveig (author)
Baas, Annette F. (author)
Giusti, Betti (author)
Strauss, Ewa (author)
van't Hof, Femke N. G. (author)
Webb, Thomas R. (author)
Erdman, Robert (author)
Ritchie, Marylyn D. (author)
Elmore, James R. (author)
Verma, Anurag (author)
Pendergrass, Sarah (author)
Kullo, Iftikhar J. (author)
Zy, Zi Ye (author)
Peissig, Peggy L. (author)
Gottesman, Omri (author)
Verma, Shefali S. (author)
Malinowski, Jennifer (author)
Rasmussen-Torvik, Laura J. (author)
Borthwick, Kenneth M. (author)
Smelser, Diane T. (author)
Crosslin, David R. (author)
de Andrade, Mariza (author)
Ryer, Evan J. (author)
McCarty, Catherine A. (author)
Bottinger, Erwin P. (author)
Pacheco, Jennifer A. (author)
Crawford, Dana C. (author)
Carrell, David S. (author)
Gerhard, Glenn S. (author)
Franklin, David P. (author)
Carey, David J. (author)
Phillips, Victoria L. (author)
Williams, Michael J. A. (author)
Wei, Wenhua (author)
Blair, Ross (author)
Hill, Andrew A. (author)
Vasudevan, Thodor M. (author)
Lewis, David R. (author)
Thomson, Ian A. (author)
Krysa, Jo (author)
Hill, Geraldine B. (author)
Roake, Justin (author)
Merriman, Tony R. (author)
Oszkinis, Grzegorz (author)
Galora, Silvia (author)
Saracini, Claudia (author)
Abbate, Rosanna (author)
Pulli, Raffaele (author)
Pratesi, Carlo (author)
Saratzis, Athanasios (author)
Verissimo, Ana R. (author)
Bumpstead, Suzannah (author)
Badger, Stephen A. (author)
Clough, Rachel E. (author)
Cockerill, Gillian (author)
Hafez, Hany (author)
Scott, D. Julian A. (author)
Futers, T. Simon (author)
Romaine, Simon P. R. (author)
Bridge, Katherine (author)
Griffin, Kathryn J. (author)
Bailey, Marc A. (author)
Smith, Alberto (author)
Thompson, Matthew M. (author)
van Bockxmeer, Frank M. (author)
Matthiasson, Stefan E. (author)
Thorleifsson, Gudmar (author)
Thorsteinsdottir, Unnur (author)
Blankensteijn, Jan D. (author)
Teijink, Joep A. W. (author)
Wijmenga, Cisca (author)
de Graaf, Jacqueline (author)
Kiemeney, Lambertus A. (author)
Lindholt, Jes S. (author)
Hughes, Anne (author)
Bradley, Declan T. (author)
Stirrups, Kathleen (author)
Golledge, Jonathan (author)
Norman, Paul E. (author)
Powell, Janet T. (author)
Humphries, Steve E. (author)
Hamby, Stephen E. (author)
Goodall, Alison H. (author)
Nelson, Christopher P. (author)
Sakalihasan, Natzi (author)
Courtois, Audrey (author)
Ferrell, Robert E. (author)
Eriksson, Per (author)
Folkersen, Lasse (author)
Franco-Cereceda, Anders (author)
Eicher, John D. (author)
Johnson, Andrew D. (author)
Betsholtz, Christer (author)
Ruusalepp, Arno (author)
Franzen, Oscar (author)
Schadt, Eric E. (author)
Bjorkegren, Johan L. M. (author)
Lipovich, Leonard (author)
Drolet, Anne M. (author)
Verhoeven, Eric L. (author)
Zeebregts, Clark J. (author)
Geelkerken, Robert H. (author)
van Sambeek, Marc R. (author)
van Sterkenburg, Steven M. (author)
de Vries, Jean-Paul (author)
Stefansson, Kari (author)
Thompson, John R. (author)
de Bakker, Paul I. W. (author)
Deloukas, Panos (author)
Sayers, Robert D. (author)
Harrison, Seamus C. (author)
van Rij, Andre M. (author)
Samani, Nilesh J. (author)
Bown, Matthew J. (author)
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 (publisher)
2017
2017
English.
In: Circulation Research. - 0009-7330. ; 120:2, 341-
  • swepub:Mat__t
Abstract Subject headings
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  • Rationale: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. Objective: To identify additional AAA risk loci using data from all available genome-wide association studies. 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). 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. Network analyses identified ERG, IL6R, and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. Conclusions: 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.

Subject headings

Medical and Health Sciences  (hsv)
Clinical Medicine  (hsv)
Hematology  (hsv)
Medicin och hälsovetenskap  (hsv)
Klinisk medicin  (hsv)
Hematologi  (hsv)
Cardiac and Cardiovascular Systems  (hsv)
Kardiologi  (hsv)

Keyword

aortic aneurysm
abdominal
computational biology
genetics
genome-wide association study
matrix metalloproteinases
meta-analysis

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By the author/editor
Jones, Gregory T ...
Tromp, Gerard
Kuivaniemi, Hele ...
Gretarsdottir, S ...
Baas, Annette F.
Giusti, Betti
show more...
Strauss, Ewa
van't Hof, Femke ...
Webb, Thomas R.
Erdman, Robert
Ritchie, Marylyn ...
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Verma, Anurag
Pendergrass, Sar ...
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Peissig, Peggy L ...
Gottesman, Omri
Verma, Shefali S ...
Malinowski, Jenn ...
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Borthwick, Kenne ...
Smelser, Diane T ...
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de Andrade, Mari ...
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McCarty, Catheri ...
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Carrell, David S ...
Gerhard, Glenn S ...
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Carey, David J.
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Williams, Michae ...
Wei, Wenhua
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Hill, Andrew A.
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Oszkinis, Grzego ...
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Abbate, Rosanna
Pulli, Raffaele
Pratesi, Carlo
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van Bockxmeer, F ...
Matthiasson, Ste ...
Thorleifsson, Gu ...
Thorsteinsdottir ...
Blankensteijn, J ...
Teijink, Joep A. ...
Wijmenga, Cisca
de Graaf, Jacque ...
Kiemeney, Lamber ...
Lindholt, Jes S.
Hughes, Anne
Bradley, Declan ...
Stirrups, Kathle ...
Golledge, Jonath ...
Norman, Paul E.
Powell, Janet T.
Humphries, Steve ...
Hamby, Stephen E ...
Goodall, Alison ...
Nelson, Christop ...
Sakalihasan, Nat ...
Courtois, Audrey
Ferrell, Robert ...
Eriksson, Per
Folkersen, Lasse
Franco-Cereceda, ...
Eicher, John D.
Johnson, Andrew ...
Betsholtz, Chris ...
Ruusalepp, Arno
Franzen, Oscar
Schadt, Eric E.
Bjorkegren, Joha ...
Lipovich, Leonar ...
Drolet, Anne M.
Verhoeven, Eric ...
Zeebregts, Clark ...
Geelkerken, Robe ...
van Sambeek, Mar ...
van Sterkenburg, ...
de Vries, Jean-P ...
Stefansson, Kari
Thompson, John R ...
de Bakker, Paul ...
Deloukas, Panos
Sayers, Robert D ...
Harrison, Seamus ...
van Rij, Andre M ...
Samani, Nilesh J ...
Bown, Matthew J.
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