Meta-analysis of genome-wide association studies for abdominal aortic aneurysm identifies four new disease-specific risk loci.
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Published version
Author(s)
Type
Journal Article
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 (GWAS). METHODS AND RESULTS: Through a meta-analysis of 6 GWAS datasets and a validation study totalling 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 SNPs and coronary artery disease, blood pressure, lipids or diabetes. 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 appear 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.
Date Issued
2016-11-29
Date Acceptance
2016-11-21
Citation
Circulation Research, 2016, 120 (2), pp.341-353
ISSN
1524-4571
Publisher
American Heart Association
Start Page
341
End Page
353
Journal / Book Title
Circulation Research
Volume
120
Issue
2
Copyright Statement
© 2016 Circulation Research is published on behalf of the American Heart Association, Inc., by Wolters Kluwer. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited.
Identifier
http://www.ncbi.nlm.nih.gov/pubmed/27899403
PII: CIRCRESAHA.116.308765
Subjects
Science & Technology
Life Sciences & Biomedicine
Cardiac & Cardiovascular Systems
Hematology
Peripheral Vascular Disease
Cardiovascular System & Cardiology
aortic aneurysm, abdominal
computational biology
genetics
genome-wide association study
matrix metalloproteinases
meta-analysis
CORONARY-ARTERY-DISEASE
DENSITY-LIPOPROTEIN CHOLESTEROL
ELECTRONIC MEDICAL-RECORDS
CANDIDATE GENE ASSOCIATION
RECEPTOR-RELATED PROTEIN-1
HUMAN PREFRONTAL CORTEX
C-REACTIVE PROTEIN
SUSCEPTIBILITY LOCI
SEQUENCE VARIANT
TRANSCRIPTION FACTORS
Aortic Aneurysm, Abdominal
Genetic Loci
Genetic Predisposition to Disease
Genetic Variation
Genome-Wide Association Study
Humans
Cardiovascular System & Hematology
1103 Clinical Sciences
1102 Cardiovascular Medicine And Haematology
Publication Status
Published
Coverage Spatial
United States