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Circ Res. 2017 Jan 20;120(2):341-353. doi: 10.1161/CIRCRESAHA.116.308765. Epub 2016 Nov 29.

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

Jones GT1, Tromp G2, Kuivaniemi H2, Gretarsdottir S2, Baas AF2, Giusti B2, Strauss E2, Van't Hof FN2, Webb TR2, Erdman R2, Ritchie MD2, Elmore JR2, Verma A2, Pendergrass S2, Kullo IJ2, Ye Z2, Peissig PL2, Gottesman O2, Verma SS2, Malinowski J2, Rasmussen-Torvik LJ2, Borthwick KM2, Smelser DT2, Crosslin DR2, de Andrade M2, Ryer EJ2, McCarty CA2, Böttinger EP2, Pacheco JA2, Crawford DC2, Carrell DS2, Gerhard GS2, Franklin DP2, Carey DJ2, Phillips VL2, Williams MJ2, Wei W2, Blair R2, Hill AA2, Vasudevan TM2, Lewis DR2, Thomson IA2, Krysa J2, Hill GB2, Roake J2, Merriman TR2, Oszkinis G2, Galora S2, Saracini C2, Abbate R2, Pulli R2, Pratesi C2, Saratzis A2, Verissimo AR2, Bumpstead S2, Badger SA2, Clough RE2, Cockerill G2, Hafez H2, Scott DJ2, Futers TS2, Romaine SP2, Bridge K2, Griffin KJ2, Bailey MA2, Smith A2, Thompson MM2, van Bockxmeer FM2, Matthiasson SE2, Thorleifsson G2, Thorsteinsdottir U2, Blankensteijn JD2, Teijink JA2, Wijmenga C2, de Graaf J2, Kiemeney LA2, Lindholt JS2, Hughes A2, Bradley DT2, Stirrups K2, Golledge J2, Norman PE2, Powell JT2, Humphries SE2, Hamby SE2, Goodall AH2, Nelson CP2, Sakalihasan N2, Courtois A2, Ferrell RE2, Eriksson P2, Folkersen L2, Franco-Cereceda A2, Eicher JD2, Johnson AD2, Betsholtz C2, Ruusalepp A2, Franzén O2, Schadt EE2, Björkegren JL2, Lipovich L2, Drolet AM2, Verhoeven EL2, Zeebregts CJ2, Geelkerken RH2, van Sambeek MR2, van Sterkenburg SM2, de Vries JP2, Stefansson K2, Thompson JR2, de Bakker PI2, Deloukas P2, Sayers RD2, Harrison SC2, van Rij AM2, Samani NJ2, Bown MJ1.

Author information

1
For the author affiliations, please see the Appendix. m.bown@le.ac.uk greg.jones@otago.ac.nz.
2
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.

KEYWORDS:

aortic aneurysm, abdominal; computational biology; genetics; genome-wide association study; matrix metalloproteinases; meta-analysis

PMID:
27899403
PMCID:
PMC5253231
DOI:
10.1161/CIRCRESAHA.116.308765
[Indexed for MEDLINE]
Free PMC Article

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