Three genome-wide studies spanning a decade, ending in the Million Veteran Program, built a 24-locus genetic map of abdominal aortic aneurysm and found a causal link to diastolic blood pressure.
Solid lines are connections this site curates. Dashed lines mean the two ends share a research paper — worth knowing, and not a claim that one explains the other.
An abdominal aortic aneurysm (AAA) is an abnormal bulging or widening of the aorta, the body's largest blood vessel, in the section that runs through the abdomen. Most AAAs cause no symptoms until they grow large enough to rupture, which is a medical emergency with a high mortality rate — the reason many countries screen older men, the group at highest risk, with a one-time ultrasound.
Gretarsdottir et al. 2010 ran a GWAS in 1,292 AAA cases and 30,503 controls from Iceland and the Netherlands, with follow-up in up to 3,267 more cases and 7,451 more controls. The study found rs7025486, near DAB2IP, associated with AAA (odds ratio 1.21) — and the same allele was also linked to early-onset heart attack, peripheral arterial disease, and pulmonary embolism, a variant with reach across multiple vascular diseases rather than one specifically.
Jones et al. 2017 meta-analysed 6 GWAS datasets plus a validation study, 10,204 cases and 107,766 controls in total, and found 4 new loci: SMYD2, LINC00540, a region near PCIF1/MMP9/ZNF335, and ERG. A separate network analysis in the same paper identified ERG, IL6R, and LDLR as modifiers of MMP9 — a gene central to the connective-tissue breakdown involved in aneurysm formation — with a direct interaction found between ERG and MMP9. This page's rs9316871, in LINC00540, is one of the paper's own four headline new loci; rs12133641, in IL6R, comes from the paper's separate network-modifier analysis rather than its four headline loci.
Klarin et al. 2020, using the Million Veteran Program, studied 7,642 cases and 172,172 controls of European ancestry, with replication in up to 4,972 more cases and 99,858 more controls. The study found 14 novel loci, bringing the total number of known AAA loci to 24. Using Mendelian randomization, it found that diastolic blood pressure — not systolic — likely has a causal relationship with AAA development, and a 29-variant polygenic risk score was strongly associated with AAA risk. This page holds five of this study's variants: near RP11-136O12.2, and in CRISPLD2, CTAGE1, LPA, and ABHD16B.
2025-10-01 · Integrative Genome-wide Association Meta-analysis of Aortic Aneurysm and Dissection Identifies Five Novel Genes. Genomics, Proteomics & Bioinformatics. 2025. DOI:10.1093/gpbjnl/qzaf039
Aortic aneurysm and dissection (AAD) subtypes had mostly been studied separately, even though earlier work suggested they share genetic mechanisms. This meta-analysis combined subtypes into one analysis of 11,148 cases and 708,468 controls of European ancestry, finding 24 susceptibility loci including 4 genuinely novel ones: PALMD (1p21.2), CRIM1 (2p22.2), FRK (6q22.1) and HMGA2 (12q14.3), partially validated in independent populations. Cell-type analysis identified artery tissue as the most relevant site of action. Gene prioritization across 53 genes reinforced elastic fiber formation and TGF-beta signaling as central AAD pathways -- both well-established in the field, now with more supporting genetic evidence. AAD was genetically correlated with various cardiovascular diseases, and risk factors like BMI, lipid levels and pulse pressure showed causal associations with AAD via Mendelian randomization. Most notably, the study went beyond statistics: 5 prioritized genes from the novel loci (PALMD, CRIM1, FRK, HMGA2, plus NT5DC1) were functionally confirmed as regulators of smooth muscle and endothelial cell function through actual ex vivo and in vitro lab experiments, not just computational prediction. This site's abdominal aortic aneurysm page carries 8 variants; none of these five genes are currently among them.
2025-09-24 · Genetic relationship between Sjögren's syndrome and abdominal aortic aneurysm: insights from a European population's genome-wide association analysis. Frontiers in Cardiovascular Medicine. 2025. DOI:10.3389/fcvm.2025.1554991
Sjögren's syndrome (SS, an autoimmune disease attacking moisture-producing glands) and abdominal aortic aneurysm (AAA) frequently coexist clinically, and this study investigated whether that reflects shared genetics rather than coincidence. Using European GWAS data (585 SS cases, 4,083 AAA cases), it found a significant positive genetic correlation (rg=0.32), 8 shared risk SNPs and 6 pleiotropic genes -- including HLA-B, HLA-DQB2 and LSM2 -- concentrated in the 6p22.2-21.32 region. Pathway analysis found strong enrichment for MHC class II antigen presentation and spliceosome/U6 snRNA binding, and tissue-specific analysis found shared heritability enrichment in artery/aorta, kidney and secretory tissues -- a genuinely coherent immune-vascular story rather than a statistical fluke. Immune cell co-localization implicated myeloid dendritic cells expressing HLA-DR (via rs9272318) in a shared dysregulation process. HLA-B itself was prioritized as a druggable target. The study's clinical suggestion: given this shared genetic and immunological basis, earlier AAA screening in Sjögren's patients may be clinically warranted, and HLA-pathway immunotherapies could theoretically address both conditions. This site's abdominal aortic aneurysm page carries 8 variants and Sjögren's syndrome page carries 3; none of HLA-B, HLA-DQB2 or LSM2 are currently on either.
AAA is diagnosed and monitored with imaging (usually ultrasound or CT), not with any variant on this page. Screening programs target people at elevated risk by age, sex, and smoking history — not genotype — because most AAAs are silent until they become dangerous.
None of the variants here changes screening guidelines or treatment decisions, which depend on aneurysm size and growth rate measured directly. The Klarin et al. 2020 finding that diastolic blood pressure specifically has a likely causal role is a research insight into disease biology, not a clinical directive on its own.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Abdominal Aortic Aneurysm comes down to these specific, well-studied positions — not a diagnosis.
The studies behind these variants recruited participants from different ancestries — a result found in one population doesn't always transfer to another. Based on 8 of 8 linked studies with a resolved discovery ancestry.
Databases, guidelines and references
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Abdominal Aortic Aneurysm. MyGeneLog™. https://www.mygenelog.com/conditions/abdominal-aortic-aneurysm
An AAA is an abnormal bulging or widening of the aorta in the abdomen. Most cause no symptoms until they grow large enough to rupture, a medical emergency, which is why older men at elevated risk are often screened with ultrasound.
Together they built a genetic map that grew from one confirmed locus (DAB2IP) in 2010 to 24 known significant loci by 2020, and found that diastolic blood pressure likely has a causal role in AAA development.
No. AAA is diagnosed and monitored with imaging, usually ultrasound or CT — not with genotype. Screening targets people by age, sex, and smoking history.
No — the same variant was also linked to early-onset heart attack, peripheral arterial disease, and pulmonary embolism in the original study, suggesting effects across multiple vascular diseases.
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