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

Authors:
Gregory T Jones Gerard Tromp Helena Kuivaniemi Solveig Gretarsdottir Annette F Baas Betti Giusti Ewa Strauss Femke N G Van't Hof Thomas R Webb Robert Erdman Marylyn D Ritchie James R Elmore Anurag Verma Sarah Pendergrass Iftikhar J Kullo Zi Ye Peggy L Peissig Omri Gottesman Shefali S Verma Jennifer Malinowski Laura J Rasmussen-Torvik Kenneth M Borthwick Diane T Smelser David R Crosslin Mariza de Andrade Evan J Ryer Catherine A McCarty Erwin P Böttinger Jennifer A Pacheco Dana C Crawford David S Carrell Glenn S Gerhard David P Franklin David J Carey Victoria L Phillips Michael J A Williams Wenhua Wei Ross Blair Andrew A Hill Thodor M Vasudevan David R Lewis Ian A Thomson Jo Krysa Geraldine B Hill Justin Roake Tony R Merriman Grzegorz Oszkinis Silvia Galora Claudia Saracini Rosanna Abbate Raffaele Pulli Carlo Pratesi Athanasios Saratzis Ana R Verissimo Suzannah Bumpstead Stephen A Badger Rachel E Clough Gillian Cockerill Hany Hafez D Julian A Scott T Simon Futers Simon P R Romaine Katherine Bridge Kathryn J Griffin Marc A Bailey Alberto Smith Matthew M Thompson Frank M van Bockxmeer Stefan E Matthiasson Gudmar Thorleifsson Unnur Thorsteinsdottir Jan D Blankensteijn Joep A W Teijink Cisca Wijmenga Jacqueline de Graaf Lambertus A Kiemeney Jes S Lindholt Anne Hughes Declan T Bradley Kathleen Stirrups Jonathan Golledge Paul E Norman Janet T Powell Steve E Humphries Stephen E Hamby Alison H Goodall Christopher P Nelson Natzi Sakalihasan Audrey Courtois Robert E Ferrell Per Eriksson Lasse Folkersen Anders Franco-Cereceda John D Eicher Andrew D Johnson Christer Betsholtz Arno Ruusalepp Oscar Franzén Eric E Schadt Johan L M Björkegren Leonard Lipovich Anne M Drolet Eric L Verhoeven Clark J Zeebregts Robert H Geelkerken Marc R van Sambeek Steven M van Sterkenburg Jean-Paul de Vries Kari Stefansson John R Thompson Paul I W de Bakker Panos Deloukas Robert D Sayers Seamus C Harrison Andre M van Rij Nilesh J Samani Matthew J Bown

Circ Res 2017 Jan 29;120(2):341-353. Epub 2016 Nov 29.

For the author affiliations, please see the Appendix.

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.

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Source
http://dx.doi.org/10.1161/CIRCRESAHA.116.308765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5253231PMC
January 2017
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1 Citation
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