rs7025486

badMag 5.5

This is a intron variant variant in the DAB2IP gene.

Key Literature Trait Associations

Abdominal Aortic Aneurysm

rs7025486 in DAB2IP is one of the strongest genetic risk factors for abdominal aortic aneurysm (AAA) identified to date, with replicated associations across AAA, early-onset coronary heart disease, and peripheral artery disease. DAB2IP suppresses TNF-NF-kB signalling in vascular smooth muscle cells; the A risk allele reduces DAB2IP expression, promoting extracellular matrix degradation and inflammatory cell infiltration in the aortic wall.

Roychowdhury T et al. “Genome-wide association meta-analysis identifies risk loci for abdominal aortic aneurysm and highlights PCSK9 as a therapeutic target.” Nature Genetics (2023)

Allele A

OR —

β 0.102 ±0.009

p 1.0e-30

N 1,125,328

Meta-analysisLarge GWAS

European

Gretarsdottir S et al. “Genome-wide association study identifies a sequence variant within the DAB2IP gene conferring susceptibility to abdominal aortic aneurysm.” Nature Genetics (2010)

Allele A

OR 1.21

p 4.6e-10

N 31,795

Large GWAS

European

Schunkert H et al. “Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease.” Nature Genetics 43(4):333-338 (2011)

Allele A

OR 1.21

p 4.6e-10

Large GWAS

Harrison SC et al. “Association of a sequence variant in DAB2IP with coronary heart disease.” European Heart Journal (2012)

Allele A

OR 1.10

p 3.2e-6

N 30,016

Meta-analysis

European

Ye Z et al. “A DAB2IP genotype: sex interaction is associated with abdominal aortic aneurysm expansion.” Journal of Investigative Medicine : the Official Publication of the American Federation for Clinical Research (2017)

Allele A

OR —

p 3.0e-3

N 650

Preliminary work

European

Nugroho NT et al. “Association of Genetic Polymorphisms with Abdominal Aortic Aneurysm in the Processes of Apoptosis, Inflammation, and Cholesterol Metabolism.” Medicina (kaunas, Lithuania) (2023)

Allele A

OR —

p 4.0e-2

N 198

Candidate gene study

European

Myocardial infarction

The rs7025486-A allele shows genome-wide significant association with myocardial infarction (MI) risk. The original 2010 AAA GWAS by Gretarsdottir et al. reported OR=1.18 for early-onset MI (p=3.1×10⁻⁵). A 2021 large-scale GWAS in ~831,000 subjects confirmed rs7025486-A as a genome-wide significant MI susceptibility locus (OR≈1.05, p=4×10⁻⁸). A Saudi–European combined meta-analysis in 2023 further replicated this signal across diverse populations. The pleiotropic effect across AAA and MI reflects DAB2IP's role in vascular smooth muscle cell survival and atherosclerotic plaque vulnerability.

Hartiala JA et al. “Genome-wide analysis identifies novel susceptibility loci for myocardial infarction.” European Heart Journal 42(9):919-933 (2021)

Allele A

OR 1.05

p 4.0e-8

N 831,000

Large GWAS

multi-ancestry

Al-Ali AK et al. “Uncovering myocardial infarction genetic signatures using GWAS exploration in Saudi and European cohorts.” Scientific Reports (2023)

Allele A

OR —

p 6.0e-8

N 640,268

Small GWAS

multi-ancestry

Gretarsdottir S et al. “Genome-wide association study identifies a sequence variant within the DAB2IP gene conferring susceptibility to abdominal aortic aneurysm.” Nature Genetics (2010)

Allele A

OR 1.18

p 3.1e-5

N 42,513

Preliminary work

European

Inflammatory Response

DAB2IP acts as a negative regulator of TNF-mediated NF-kB signalling in vascular endothelial and smooth muscle cells. The A allele at rs7025486 reduces DAB2IP expression, disinhibiting NF-kB and amplifying local vascular inflammatory responses. Functional knockout models show this produces elevated plasma TNF, IL-6, and IL-12, increased monocyte adhesion to the endothelium, and accelerated atherosclerosis — consistent with the SNP's association with multiple vascular diseases.

Allele A

OR —

p 4.0e-2

N 198

Candidate gene study

European

Huang Q et al. “AIP1 suppresses atherosclerosis by limiting hyperlipidemia-induced inflammation and vascular endothelial dysfunction.” Arteriosclerosis, Thrombosis, and Vascular Biology (2013)

Allele A

OR —

p —

Preliminary work

Roychowdhury T et al. “Genome-wide association meta-analysis identifies risk loci for abdominal aortic aneurysm and highlights PCSK9 as a therapeutic target.” Nature Genetics (2023)

Allele A

OR —

β 0.102 ±0.009

p 1.0e-30

N 1,125,328

Meta-analysisLarge GWAS

European

Coronary artery disease

The rs7025486-A allele has been associated with premature coronary artery disease (CAD) in multiple smaller studies. An Indian population study found the AA homozygous genotype conferred OR=3.15 for CAD onset before age 50 (p=0.034), while a Pakistani GWAS-risk-score study found rs7025486 contributed significantly to a cumulative 21-variant CAD risk score. However, a Chinese Han population study found no significant association, indicating population-specific effects. The variant's contribution to CAD likely reflects shared mechanisms with the established MI and AAA associations through DAB2IP-mediated vascular smooth muscle cell apoptosis and inflammatory dysregulation.

Bhanushali AA et al. “Frequency and association of disabled homolog 2-interacting protein (DAB2IP) variant rs7025486 G>A with coronary artery disease risk in Indian population.” Indian Heart Journal (2018)

Allele A

OR 3.15

p 3.4e-2

N 339

Candidate gene study

South Asian

Shahid SU et al. “Genetic risk analysis of coronary artery disease in Pakistani subjects using a genetic risk score of 21 variants.” Atherosclerosis (2017)

Allele A

OR —

p —

Candidate gene study

South Asian

Body mass index

The rs7025486-G allele reached genome-wide significance for higher BMI in a 2022 Nature Communications phenome-wide GWAS of approximately 1.1 million European-ancestry participants (β=0.0089 SD units per copy, SE=0.0015, p=4×10⁻⁹). The effect size is modest and the direction of the risk allele is opposite to the AAA-risk A allele, suggesting independent or opposing regulatory effects at this locus. This BMI association may contribute to the complex cardiometabolic phenome of DAB2IP variation, given BMI's downstream influence on vascular disease risk.

Huang J et al. “Genomics and phenomics of body mass index reveals a complex disease network.” Nature Communications 13(1):7973 (2022)

Allele G

OR —

β 0.009 ±0.002

p 4.0e-9

N 1,122,049

Large GWAS

European

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GWAS Catalog Trait Associations (2)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

rs7025486

Key Literature Trait Associations

Abdominal Aortic Aneurysm

Myocardial infarction

Inflammatory Response

Coronary artery disease

Body mass index

GWAS Catalog Trait Associations (2)

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