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Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci
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 geno...
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Lippincott Williams & Wilkins
2017
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5253231/ https://www.ncbi.nlm.nih.gov/pubmed/27899403 http://dx.doi.org/10.1161/CIRCRESAHA.116.308765 |
| _version_ | 1782498139744239616 |
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| author | 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, Diane 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. Julian A. Futers, T. 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. Bown, Matthew J. |
| author_facet | 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, Diane 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. Julian A. Futers, T. 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. Bown, Matthew J. |
| author_sort | Jones, Gregory T. |
| collection | PubMed |
| description | 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. |
| format | Online Article Text |
| id | pubmed-5253231 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2017 |
| publisher | Lippincott Williams & Wilkins |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-52532312017-02-08 Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci 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, Diane 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. Julian A. Futers, T. 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. Bown, Matthew J. Circ Res Clinical Track 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. Lippincott Williams & Wilkins 2017-01-20 2017-01-19 /pmc/articles/PMC5253231/ /pubmed/27899403 http://dx.doi.org/10.1161/CIRCRESAHA.116.308765 Text en © 2016 The Authors. Circulation Research is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited. |
| spellingShingle | Clinical Track 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, Diane 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. Julian A. Futers, T. 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. Bown, Matthew J. Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci |
| title | Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci |
| title_full | Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci |
| title_fullStr | Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci |
| title_full_unstemmed | Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci |
| title_short | Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci |
| title_sort | meta-analysis of genome-wide association studies for abdominal aortic aneurysm identifies four new disease-specific risk loci |
| topic | Clinical Track |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5253231/ https://www.ncbi.nlm.nih.gov/pubmed/27899403 http://dx.doi.org/10.1161/CIRCRESAHA.116.308765 |
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AT schadterice metaanalysisofgenomewideassociationstudiesforabdominalaorticaneurysmidentifiesfournewdiseasespecificriskloci AT bjorkegrenjohanlm metaanalysisofgenomewideassociationstudiesforabdominalaorticaneurysmidentifiesfournewdiseasespecificriskloci AT lipovichleonard metaanalysisofgenomewideassociationstudiesforabdominalaorticaneurysmidentifiesfournewdiseasespecificriskloci AT droletannem metaanalysisofgenomewideassociationstudiesforabdominalaorticaneurysmidentifiesfournewdiseasespecificriskloci AT verhoevenericl metaanalysisofgenomewideassociationstudiesforabdominalaorticaneurysmidentifiesfournewdiseasespecificriskloci AT zeebregtsclarkj metaanalysisofgenomewideassociationstudiesforabdominalaorticaneurysmidentifiesfournewdiseasespecificriskloci AT geelkerkenroberth metaanalysisofgenomewideassociationstudiesforabdominalaorticaneurysmidentifiesfournewdiseasespecificriskloci AT vansambeekmarcr metaanalysisofgenomewideassociationstudiesforabdominalaorticaneurysmidentifiesfournewdiseasespecificriskloci AT vansterkenburgstevenm metaanalysisofgenomewideassociationstudiesforabdominalaorticaneurysmidentifiesfournewdiseasespecificriskloci AT devriesjeanpaul metaanalysisofgenomewideassociationstudiesforabdominalaorticaneurysmidentifiesfournewdiseasespecificriskloci AT stefanssonkari metaanalysisofgenomewideassociationstudiesforabdominalaorticaneurysmidentifiesfournewdiseasespecificriskloci AT thompsonjohnr metaanalysisofgenomewideassociationstudiesforabdominalaorticaneurysmidentifiesfournewdiseasespecificriskloci AT debakkerpauliw metaanalysisofgenomewideassociationstudiesforabdominalaorticaneurysmidentifiesfournewdiseasespecificriskloci AT deloukaspanos metaanalysisofgenomewideassociationstudiesforabdominalaorticaneurysmidentifiesfournewdiseasespecificriskloci AT sayersrobertd metaanalysisofgenomewideassociationstudiesforabdominalaorticaneurysmidentifiesfournewdiseasespecificriskloci AT harrisonseamusc metaanalysisofgenomewideassociationstudiesforabdominalaorticaneurysmidentifiesfournewdiseasespecificriskloci AT vanrijandrem metaanalysisofgenomewideassociationstudiesforabdominalaorticaneurysmidentifiesfournewdiseasespecificriskloci AT samaninileshj metaanalysisofgenomewideassociationstudiesforabdominalaorticaneurysmidentifiesfournewdiseasespecificriskloci AT bownmatthewj metaanalysisofgenomewideassociationstudiesforabdominalaorticaneurysmidentifiesfournewdiseasespecificriskloci AT metaanalysisofgenomewideassociationstudiesforabdominalaorticaneurysmidentifiesfournewdiseasespecificriskloci |