Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci
Authors: 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. 
Published: November 2016

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.