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Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci
Univ Otago, Dept Surg, Dunedin 9054, New Zealand..
Geisinger Hlth Syst, Sigfried & Janet Weis Ctr Res, Danville, PA USA.;Univ Stellenbosch, Dept Biomed Sci, Fac Med & Hlth Sci, Div Mol Biol & Human Genet, Tygerberg, South Africa.;deCODE Amgen, Reykjavik, Iceland..
Geisinger Hlth Syst, Sigfried & Janet Weis Ctr Res, Danville, PA USA.;Univ Stellenbosch, Dept Biomed Sci, Fac Med & Hlth Sci, Div Mol Biol & Human Genet, Tygerberg, South Africa..
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2017 (English)In: Circulation Research, ISSN 0009-7330, E-ISSN 1524-4571, Vol. 120, no 2, p. 341-+Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2017. Vol. 120, no 2, p. 341-+
Keywords [en]
aortic aneurysm, abdominal, computational biology, genetics, genome-wide association study, matrix metalloproteinases, meta-analysis
National Category
Hematology Cardiac and Cardiovascular Systems
Identifiers
URN: urn:nbn:se:uu:diva-316025DOI: 10.1161/CIRCRESAHA.116.308765ISI: 000392226200017PubMedID: 27899403OAI: oai:DiVA.org:uu-316025DiVA, id: diva2:1076926
Funder
Wellcome trust, 076113 085475Swedish Research CouncilSwedish Heart Lung FoundationTorsten Söderbergs stiftelseRagnar Söderbergs stiftelseKnut and Alice Wallenberg FoundationNIH (National Institute of Health), R01HL71207EU, European Research Council, ETF 8853Available from: 2017-02-24 Created: 2017-02-24 Last updated: 2017-11-29Bibliographically approved

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