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.; Zi, Ye; 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.

doi:10.1161/CIRCRESAHA.116.308765

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.

trova@unifi

Titolo:	Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci
Autori di Ateneo:	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. mostra contributor esterni nascondi contributor esterni
Autori:	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.
Data di pubblicazione:	2017
Rivista:	CIRCULATION RESEARCH
Volume:	120
Pagina iniziale:	341
Pagina finale:	353
Abstract:	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.
Handle:	http://hdl.handle.net/2158/1084753
Appare nelle tipologie:	1a - Articolo su rivista

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