Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci
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Published:2017-01-20
Issue:2
Volume:120
Page:341-353
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ISSN:0009-7330
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Container-title:Circulation Research
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language:en
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Short-container-title:Circ Res
Author:
Jones Gregory T.1, Tromp Gerard1, Kuivaniemi Helena1, Gretarsdottir Solveig1, Baas Annette F.1, Giusti Betti1, Strauss Ewa1, van‘t Hof Femke N.G.1, Webb Thomas R.1, Erdman Robert1, Ritchie Marylyn D.1, Elmore James R.1, Verma Anurag1, Pendergrass Sarah1, Kullo Iftikhar J.1, Ye Zi1, Peissig Peggy L.1, Gottesman Omri1, Verma Shefali S.1, Malinowski Jennifer1, Rasmussen-Torvik Laura J.1, Borthwick Kenneth M.1, Smelser Diane T.1, Crosslin David R.1, de Andrade Mariza1, Ryer Evan J.1, McCarty Catherine A.1, Böttinger Erwin P.1, Pacheco Jennifer A.1, Crawford Dana C.1, Carrell David S.1, Gerhard Glenn S.1, Franklin David P.1, Carey David J.1, Phillips Victoria L.1, Williams Michael J.A.1, Wei Wenhua1, Blair Ross1, Hill Andrew A.1, Vasudevan Thodor M.1, Lewis David R.1, Thomson Ian A.1, Krysa Jo1, Hill Geraldine B.1, Roake Justin1, Merriman Tony R.1, Oszkinis Grzegorz1, Galora Silvia1, Saracini Claudia1, Abbate Rosanna1, Pulli Raffaele1, Pratesi Carlo1, Saratzis Athanasios1, Verissimo Ana R.1, Bumpstead Suzannah1, Badger Stephen A.1, Clough Rachel E.1, Cockerill Gillian1, Hafez Hany1, Scott D. Julian A.1, Futers T. Simon1, Romaine Simon P.R.1, Bridge Katherine1, Griffin Kathryn J.1, Bailey Marc A.1, Smith Alberto1, Thompson Matthew M.1, van Bockxmeer Frank M.1, Matthiasson Stefan E.1, Thorleifsson Gudmar1, Thorsteinsdottir Unnur1, Blankensteijn Jan D.1, Teijink Joep A.W.1, Wijmenga Cisca1, de Graaf Jacqueline1, Kiemeney Lambertus A.1, Lindholt Jes S.1, Hughes Anne1, Bradley Declan T.1, Stirrups Kathleen1, Golledge Jonathan1, Norman Paul E.1, Powell Janet T.1, Humphries Steve E.1, Hamby Stephen E.1, Goodall Alison H.1, Nelson Christopher P.1, Sakalihasan Natzi1, Courtois Audrey1, Ferrell Robert E.1, Eriksson Per1, Folkersen Lasse1, Franco-Cereceda Anders1, Eicher John D.1, Johnson Andrew D.1, Betsholtz Christer1, Ruusalepp Arno1, Franzén Oscar1, Schadt Eric E.1, Björkegren Johan L.M.1, Lipovich Leonard1, Drolet Anne M.1, Verhoeven Eric L.1, Zeebregts Clark J.1, Geelkerken Robert H.1, van Sambeek Marc R.1, van Sterkenburg Steven M.1, de Vries Jean-Paul1, Stefansson Kari1, Thompson John R.1, de Bakker Paul I.W.1, Deloukas Panos1, Sayers Robert D.1, Harrison Seamus C.1, van Rij Andre M.1, Samani Nilesh J.1, Bown Matthew J.1
Affiliation:
1. For the author affiliations, please see the Appendix.
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.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine,Physiology
Cited by
167 articles.
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