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

Gregory T Jones; Gerard Tromp; Helena Kuivaniemi; Solveig Gretarsdottir; Annette F Baas; Betti Giusti; Ewa Strauss; Femke N van 't Hof; Thomas Webb; Robert Erdman; Jes S. Lindholt; Lasse Folkersen

doi:10.1161/CIRCRESAHA.116.308765

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

Gregory T Jones, Gerard Tromp, Helena Kuivaniemi, Solveig Gretarsdottir, Annette F Baas, Betti Giusti, Ewa Strauss, Femke N van 't Hof, Thomas Webb, Robert Erdman, Jes S. Lindholt, Lasse Folkersen

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Abstract

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. To identify additional AAA risk loci using data from all available genome-wide association studies (GWAS). 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. 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.

Original language	English
Article number	116.308765
Journal	Circulation Research
Volume	120
Pages (from-to)	341-353
Number of pages	91
ISSN	0009-7330
DOIs	https://doi.org/10.1161/CIRCRESAHA.116.308765
Publication status	Published - 2017

Bibliographical note

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.
For full list of authors, see https://doi.org/10.1161/CIRCRESAHA.116.308765

Keywords

Abdominal aortic aneurysm
Genetics
Meta-analysis
Matrix metalloproteinases
Genome-wide association studies
Bioinformatics tools

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Jones, G. T., Tromp, G., Kuivaniemi, H., Gretarsdottir, S., Baas, A. F., Giusti, B., Strauss, E., van 't Hof, F. N., Webb, T., Erdman, R., Lindholt, J. S., & Folkersen, L. (2017). Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci. Circulation Research, 120, 341-353. Article 116.308765. https://doi.org/10.1161/CIRCRESAHA.116.308765

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title = "Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci",

abstract = "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. To identify additional AAA risk loci using data from all available genome-wide association studies (GWAS). 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. 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.",

keywords = "Abdominal aortic aneurysm, Genetics, Meta-analysis, Matrix metalloproteinases, Genome-wide association studies, Bioinformatics tools",

author = "Jones, {Gregory T} and Gerard Tromp and Helena Kuivaniemi and Solveig Gretarsdottir and Baas, {Annette F} and Betti Giusti and Ewa Strauss and {van 't Hof}, {Femke N} and Thomas Webb and Robert Erdman and Lindholt, {Jes S.} and Lasse Folkersen",

note = "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. For full list of authors, see https://doi.org/10.1161/CIRCRESAHA.116.308765 ",

year = "2017",

doi = "10.1161/CIRCRESAHA.116.308765",

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Jones, GT, Tromp, G, Kuivaniemi, H, Gretarsdottir, S, Baas, AF, Giusti, B, Strauss, E, van 't Hof, FN, Webb, T, Erdman, R, Lindholt, JS & Folkersen, L 2017, 'Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci', Circulation Research, vol. 120, 116.308765, pp. 341-353. https://doi.org/10.1161/CIRCRESAHA.116.308765

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T1 - Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci

AU - Jones, Gregory T

AU - Tromp, Gerard

AU - Kuivaniemi, Helena

AU - Gretarsdottir, Solveig

AU - Baas, Annette F

AU - Giusti, Betti

AU - Strauss, Ewa

AU - van 't Hof, Femke N

AU - Webb, Thomas

AU - Erdman, Robert

AU - Lindholt, Jes S.

AU - Folkersen, Lasse

N1 - 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. For full list of authors, see https://doi.org/10.1161/CIRCRESAHA.116.308765

PY - 2017

Y1 - 2017

N2 - 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. To identify additional AAA risk loci using data from all available genome-wide association studies (GWAS). 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. 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.

AB - 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. To identify additional AAA risk loci using data from all available genome-wide association studies (GWAS). 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. 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.

KW - Abdominal aortic aneurysm

KW - Genetics

KW - Meta-analysis

KW - Matrix metalloproteinases

KW - Genome-wide association studies

KW - Bioinformatics tools

U2 - 10.1161/CIRCRESAHA.116.308765

DO - 10.1161/CIRCRESAHA.116.308765

M3 - Journal article

C2 - 27899403

SN - 0009-7330

VL - 120

SP - 341

EP - 353

JO - Circulation Research

JF - Circulation Research

M1 - 116.308765

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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