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

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posted on 2016-12-19, 15:55 authored by G. T. Jones, G. Tromp, H. Kuivaniemi, S. Gretarsdottir, A. F. Baas, B. Giusti, E. Strauss, F. N. van 't Hof, T. Webb, R. Erdman, M. D. Ritchie, Z. Ye, P. L. Peissig, O. Gottesman, S. S. Verma, J. Malinowski, L. J. Rasmussen-Torvik, K. Borthwick, D. T. Smelser, D. R. Crosslin, M. de Andrade, D. P. Franklin, E. J. Ryer, C. A. McCarty, E. P. Bottinger, J. A. Pacheco, D. C. Crawford, D. S. Carrell, G. S. Gerhard, D. J. Carey, V. L. Phillips, M. J. Williams, W. Wei, R. Blair, A. A. Hill, T. M. Vasudevan, D. R. Lewis, I. A. Thomson, R. Abbate, J. Krysa, G. B. Hill, J. Roake, T. R. Merriman, G. Oszkinis, S. Galora, C. Saracini, R. Pulli, C. Pratesi, Athanasios Saratzis, A. Verissimo, S. J. Bumpstead, S. A. Badger, R. E. Clough, G. W. Cockerill, H. Hafez, M. M. Thompson, D. J. Scott, T. S. Futers, S. P. Romaine, K. Bridge, K. J. Griffin, M. A. Bailey, A. Smith, F. van Bockxmeer, S. E. Matthiasson, G. Thorleifsson, U. Thorsteinsdottir, J. D. Blankensteijn, J. A. Teijink, C. Wijmenga, J. de Graaf, L. A. Kiemeney, S. E. Humphries, J. S. Lindholt, A. E. Hughes, D. T. Bradley, K. Stirrups, J. Golledge, P. E. Norman, J. T. Powell, S. E. Hamby, A. H. Goodall, C. P. Nelson, N. Sakalihasan, A. Courtois, R. E. Ferrell, P. Eriksson, L. Folkersen, A. Franco-Cereceda, L. Lipovich, J. D. Eicher, A. D. Johnson, C. Betsholtz, A. Ruusalepp, O. Franzén, E. Schadt, J. L. Björkegren, A. M. Drolet, E. Verhoeven, C. J. Zeebregts, R. H. Geelkerken, M. R. van Sambeek, S. M. van Sterkenburg, J. P. de Vries, K. Stefansson, J. R. Thompson, J. R. Elmore, P. I. de Bakker, P. Deloukas, R. D. Sayers, S. Harrison, A. M. van Rij, Nilesh J. Samani, Matthew J. Bown, A. Verma, S. Pendergrass, I. J. Kullo
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 (GWAS). Methods and Results: Through a meta-analysis of 6 GWAS datasets and a validation study totalling 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 SNPs and coronary artery disease, blood pressure, lipids or diabetes. 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 appear 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.

History

Citation

Circulation Research, 2017, 120 (2), pp. 341-353

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicine/Department of Cardiovascular Sciences

Version

  • VoR (Version of Record)

Published in

Circulation Research

Publisher

American Heart Association

issn

0009-7330

eissn

1524-4571

Acceptance date

2016-11-21

Copyright date

2017

Available date

2016-12-19

Publisher version

http://circres.ahajournals.org/content/120/2/341

Language

en

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