Aortic Aneurysm

Introduction

Background

An aortic aneurysm is a localized, abnormal dilation of the aorta, the largest artery in the body, to at least 1.5 times its normal diameter. These weakened areas in the aortic wall can occur anywhere along the aorta, but are most commonly found in the abdomen (abdominal aortic aneurysm, AAA) or the chest (thoracic aortic aneurysm, TAA). AAA is a common condition, responsible for approximately 13,000 deaths annually in the USA and disproportionately affects white populations.^[1]

Biological Basis

The formation of an aortic aneurysm is a complex process involving the weakening and degeneration of the aortic wall, influenced by a combination of genetic and environmental factors. A strong family history is a significant risk factor, with individuals having a first-degree relative affected by AAA showing a 2- to 11-fold increased risk.^[1] The heritability of AAA has been estimated to be as high as 70%.^[1]Genome-wide association studies (GWAS) have identified several genetic variants associated with aneurysm susceptibility. For instance, a variant in theLRP1(low-density lipoprotein receptor-related protein 1) gene is associated with abdominal aortic aneurysm.^[1] Another sequence variant within the DAB2IP gene has been found to confer susceptibility to AAA.^[2] For thoracic aortic aneurysms and aortic dissections, a susceptibility locus spanning FBN1at 15q21.1 has been identified, with specific single nucleotide polymorphisms (SNPs) likers1036477 , rs2118181 , and rs636178 showing significant associations.^[3]Furthermore, research indicates shared genetic risk factors across different aneurysm types, including intracranial, abdominal, and thoracic aneurysms. For example, a variant on 9p21 is associated with myocardial infarction, AAA, and intracranial aneurysm.^[4] Other shared loci include 18q11, 15q21, and 2q33.^[5]Recent meta-analyses of GWAS have also pinpointed four new disease-specific risk loci for AAA.^[6]

Clinical Relevance

Aortic aneurysms are clinically significant due to their potential for rupture or dissection, which are life-threatening events requiring immediate medical intervention. Rupture of a large aneurysm can lead to severe internal bleeding and is often fatal. Early detection through screening, particularly for AAA, is crucial for timely management and improved outcomes. Aortic calcification, a related condition, is an important independent predictor of future cardiovascular events.^[7]

Social Importance

The prevalence and life-threatening nature of aortic aneurysms pose a considerable public health burden, especially in aging populations. Screening programs, particularly for abdominal aortic aneurysms, have been implemented in various regions to identify individuals at risk, allowing for surveillance or elective repair before rupture occurs. Understanding the genetic underpinnings of aneurysms is vital for risk stratification, potentially leading to targeted screening, preventive strategies, and personalized treatment approaches, thereby reducing morbidity and mortality associated with this condition.

Limitations

Genetic research into aortic aneurysm has significantly advanced the understanding of its underlying mechanisms; however, several limitations warrant consideration when interpreting the findings. These limitations span methodological aspects, generalizability, and the complexity of genetic and environmental interactions. Acknowledging these constraints helps contextualize current knowledge and highlights avenues for future research.

Methodological and Statistical Considerations

The precision and robustness of genetic associations in aortic aneurysm are influenced by various methodological and statistical factors. While large-scale genome-wide association studies (GWAS) can involve hundreds of thousands of individuals, the specific case numbers for distinct aneurysm subtypes, such as abdominal aortic aneurysm (AAA) or thoracic aortic aneurysm (TAA), are often considerably smaller . Variants such asrs1333047 , rs10757279 , and rs4977575 in this region are considered strong hits for AAA risk. CDKN2B-AS1 is thought to regulate the expression of neighboring tumor suppressor genes, CDKN2A and CDKN2B, which are crucial for cell cycle control and cellular senescence, processes integral to vascular remodeling and the pathogenesis of aneurysms.^[8]Altered regulation of these genes can lead to abnormal proliferation and survival of vascular smooth muscle cells, contributing to the weakening of the aortic wall.

Other significant variants include those near LINC00540 and LRP1. LINC00540 is a long intergenic non-coding RNA, and variants like rs12857403 , rs12875918 , and rs9510086 are associated with its activity.^[6] This lincRNA has a predicted distal target, FGF9, a growth factor whose mRNA expression is notably increased in AAA tissue, suggesting its involvement in the pathological remodeling of the aorta.^[6] Meanwhile, the LRP1(Low-Density Lipoprotein Receptor-Related Protein 1) gene, involved in lipid metabolism and extracellular matrix turnover, harbors the variantrs11172113 , which has been linked to abdominal aortic aneurysm.^[1] Additionally, the rs4936098 variant near ADAMTS8(ADAM Metallopeptidase With Thrombospondin Type 1 Motif 8), an enzyme involved in extracellular matrix degradation, has been associated with blood pressure traits, a known risk factor for aneurysm formation.^[9] Variants in genes like APOE, LPA, and ZNF335also contribute to aneurysm risk. Thers429358 variant in APOE(Apolipoprotein E) is a well-established genetic factor impacting lipid metabolism and inflammatory responses, both of which are critical in the development and progression of aortic disease. Similarly, thers10455872 variant in LPA(Lipoprotein A) is strongly associated with elevated levels of lipoprotein(a), an independent risk factor for atherosclerosis and cardiovascular events that can predispose to aneurysms. Thers3827066 variant near ZNF335 (Zinc Finger Protein 335) has shown an association with phospholipid transfer protein (PLTP) expression in aortic tissue, with PLTP levels being significantly higher in aneurysmal tissue.^[6] Furthermore, the rs10736085 variant in PLCE1 (Phospholipase C Epsilon 1) is also linked to PLTPactivity, highlighting the role of lipid metabolism in aneurysm pathology.^[10] Variants like rs964184 in ZPR1 (Zinc Finger Protein, Recombinant 1) and rs1106370 near SPSB1 and LINC02606may also influence cellular processes and immune responses relevant to aortic aneurysm development.

Often Asymptomatic and Incidental Detection

Aortic aneurysms frequently present without overt symptoms, posing a diagnostic challenge until advanced stages. Many abdominal aortic aneurysms (AAA) are discovered incidentally during routine physical examinations or imaging procedures performed for unrelated medical conditions, underscoring the diagnostic value of screening in at-risk populations .

Genetic Predisposition and Molecular Regulation

Aortic aneurysm formation has a significant genetic component, with familial tendencies indicating inherited susceptibility.^[11]Genome-wide association studies (GWAS) have identified several genetic risk variants associated with the condition. For example, a sequence variant on chromosome 9p21 is consistently linked to an increased risk for abdominal aortic aneurysm (AAA), intracranial aneurysm, and myocardial infarction.^[4]Specific genes implicated in aneurysm susceptibility includeDAB2IP, where a variant confers susceptibility to AAA.^[2] and LRP1, which is associated with AAA and plays a role in vascular protection by regulating factors like CTGF and HtrA1.^[1] Variants in LRP1 and ULK4have been specifically associated with aortic disease.^[12] Molecular regulatory networks are disrupted in aneurysmal tissue, as evidenced by differential gene expression patterns.^[13] Transcription factors such as ELF1, ETS2, RUNX1, and STAT5 show altered binding activity in human AAA, influencing the expression of genes critical for vascular health.^[14] The ERG gene, involved in the embryonic development of the aorta, is hypothesized to influence AAA development and regulates the expression of matrix metalloproteinase 9 (MMP9).^[6] Furthermore, the SMYD2 gene regulates HSP90 methylation, and inhibiting HSP90 has been shown to reduce AAA formation in animal models, suggesting a role for SMYD2in disease pathogenesis and possiblyin utero aortic development.^[6] The long noncoding RNA ANRIL (CDKN2BAS1) has also been identified as a strong genetic locus associated with AAA.^[6]

Extracellular Matrix Degradation and Remodeling

The structural integrity of the aortic wall is critically dependent on a healthy extracellular matrix (ECM), a network of proteins providing strength and elasticity. Aortic aneurysm development is fundamentally driven by abnormal ECM remodeling and excessive degradation, leading to progressive weakening and dilation of the arterial wall.^[15] Key structural components, including elastic and collagen fibers, are maintained by enzymes like lysyl oxidase (LOX), which is essential for their cross-linking and integrity. Inactivation of the LOXgene in mice results in aortic aneurysms, cardiovascular dysfunction, and even perinatal death.^[16]The degradation of the ECM is primarily mediated by various matrix-degrading enzymes, such as lysosomal cysteine cathepsins, which are known for their roles in tissue remodeling.^[15] This enzymatic activity is often dysregulated, leading to an imbalance where degradation outpaces synthesis and repair. Network analyses have highlighted a central role for matrix metalloproteinase 9 (MMP9) in AAA pathogenesis, demonstrating direct or secondary interactions between MMP9 and several genes associated with AAA, underscoring its critical involvement in the breakdown of the aortic wall.^[6]Disruptions in this delicate balance, often influenced by hemodynamic stress and growth factors, are central to the pathophysiological processes of aneurysm formation.^[15]

Cellular Signaling and Inflammatory Responses

Cellular signaling pathways are integral to the initiation and progression of aortic aneurysms. The mitogen-activated protein kinase (MAPK) signaling pathway, for instance, is mediated by genes like MINK1, which also plays a role in platelet activation and thrombus formation.^[15]The presence of intraluminal thrombi, formed through platelet activation, is a known contributor to aneurysm growth and rupture, particularly in abdominal aortic aneurysms.^[15]Inflammation is a prominent feature of aneurysm pathogenesis, leading some researchers to describe aortic aneurysms as an immune disease with a strong genetic component.^[17]Vascular remodeling, a process of structural changes in blood vessel walls, is closely linked with inflammatory processes in aneurysm development.^[18] Growth factors, such as transforming growth factor-beta (TGF-β), are critical regulators of vascular cell behavior. Mutations in the TGF-β receptor (TGFBR2) can significantly alter smooth muscle cell phenotype, predisposing individuals to thoracic aortic aneurysms and dissections.^[19] These disruptions in signaling pathways contribute to the chronic inflammatory state and cellular dysfunction observed within the aneurysmal wall.

Vascular Wall Integrity and Systemic Pathophysiology

The overall integrity of the aortic wall relies on the proper function and interaction of its cellular and structural components, primarily smooth muscle cells and endothelial cells. Endothelial injury, often triggered by hemodynamic stress, is a key event that initiates and exacerbates the process of aneurysm formation.^[15]Mutations in genes encoding structural proteins, such as smooth muscle alpha-actin (ACTA2), directly impair smooth muscle cell function and are a known cause of thoracic aortic aneurysms and dissections.^[12]Genetic variants that promote abnormal smooth muscle cell proliferation can also lead to a spectrum of diffuse vascular diseases, indicative of a hyperplastic vasculomyopathy.^[20]Aortic aneurysms exhibit site specificity, meaning the disease manifests with distinct characteristics depending on its location along the aorta, highlighting the influence of localized mechanical forces and tissue interactions in disease progression.^[21]The underlying pathophysiology extends beyond the localized lesion, with systemic consequences affecting overall cardiovascular health. Furthermore, the embryonic development of the aorta is a critical factor, and aberrations duringin uteroaortic development are hypothesized to influence the risk of aortic disease later in life.^[6]These complex interactions at the tissue and organ level underscore the multifactorial nature of aortic aneurysm disease.

Extracellular Matrix Degradation and Remodeling

The structural integrity of the aortic wall is critically dependent on its extracellular matrix (ECM), and its degradation is a central mechanism in aortic aneurysm (AAA) pathogenesis. Network analysis has identifiedMMP9 (Matrix Metalloproteinase 9) as a key player, demonstrating direct interactions with ERG (ETS-related gene) and modifications by IL6R (Interleukin-6 Receptor) and LDLR(Low-density lipoprotein receptor).^[6] Overexpression of proangiogenic MMPs is strongly associated with AAA rupture, indicating their role in pathological ECM breakdown and the resulting weakening of the aortic wall.^[22] This proteolytic activity leads to the progressive dilation characteristic of aneurysms, where the balance between ECM synthesis and degradation is severely disrupted.

The enzyme lysyl oxidase (LOX) is essential for the proper cross-linking of elastic and collagen fibers, which are vital components of the aortic ECM. Inactivation of the LOXgene in mice leads to the development of aortic aneurysms and cardiovascular dysfunction, underscoring its functional significance in maintaining vascular tissue integrity.^[23] Furthermore, LRP1(Low-density lipoprotein receptor-related protein 1) plays a protective role in the vasculature by regulating the levels of connective tissue growth factor (CTGF) and HtrA1.^[24] Genetic variants in LRP1are associated with AAA, suggesting its involvement in modulating ECM composition and stability, thereby influencing aneurysm susceptibility.^[1]

Intracellular Signaling and Cell Fate Regulation

Aortic aneurysm formation involves the dysregulation of several intracellular signaling cascades that govern cell proliferation, survival, and differentiation. ThePI3K-Akt signaling pathway is pivotal in the vascular endothelium, influencing endothelial cell proliferation, survival, migration, and the production of nitric oxide, all critical for vascular homeostasis.^[2] Conversely, the JNK (c-Jun N-terminal kinase) pathway has been implicated in AAA pathogenesis, and therapeutic inhibition of JNKhas been shown to attenuate aneurysm formation in murine models, highlighting its role as a potential therapeutic target.^[2] Receptor-mediated signaling also plays a crucial role, with DAB2IP functioning as an endogenous inhibitor of VEGFR2 (Vascular Endothelial Growth Factor Receptor 2)-mediated signaling, which is an important regulator of angiogenesis.^[2] The ERG transcription factor, involved in the embryonic development of the aorta, regulates the expression of MMP9, linking developmental pathways to ECM remodeling in adult disease.^[6] Additionally, post-translational modifications, such as the methylation of HSP90 (Heat Shock Protein 90) by SMYD2, are significant, as inhibition of HSP90 can reduce AAA formation, suggesting a pathway for therapeutic intervention.^[6] The TGF-beta signaling pathway is also implicated, with mutations in its receptor, TGFBR2, altering smooth muscle cell phenotype and predisposing individuals to thoracic aortic aneurysms.^[1] MINK1further contributes to mitogen-activated protein kinase signaling and platelet activation, processes that contribute to aneurysm growth and rupture.^[15]

Genetic and Epigenetic Control of Aortic Homeostasis

Genetic predisposition is a strong determinant in the development of aortic aneurysms, with numerous susceptibility loci identified through genome-wide association studies (GWAS).^[6] These genetic variants often function as expression quantitative trait loci (eQTLs), impacting the transcriptional activity and expression levels of proximal genes, thereby influencing protein abundance and cellular functions within the aortic wall.^[6] For example, PLTP(Phospholipid transfer protein) expression is significantly higher in aneurysmal aortic tissue, suggesting that genetically influenced alterations in lipid metabolism contribute to aneurysm pathology.^[6] The activity of the PON1 (Paraoxonase 1) enzyme and its genetic variants also influence PLTPactivity, highlighting a regulatory link between antioxidant defense and lipid metabolism in the context of aortic health.^[6] Transcriptional regulation is meticulously controlled by transcription factors (TFs) such as ELF1, ETS2, RUNX1, and STAT5, whose binding profiles exhibit differences between aneurysmal and healthy aortic tissue.^[6] Specifically, ETS factors are known to regulate Vegf-dependent arterial specification, underscoring their critical role in vascular development and maintenance.^[6] The long noncoding RNA ANRIL (CDKN2BAS1), identified as a strong hit in GWAS, further illustrates the complex interplay of epigenetic and transcriptional regulatory mechanisms that govern aortic homeostasis and disease susceptibility.^[6] Mutations in genes encoding structural proteins, such as ACTA2(smooth muscle alpha-actin) andFBN1 (Fibrillin-1), directly compromise the structural integrity of the aorta, leading to aneurysms and dissections.^[1]

Inflammatory and Immune System Contributions

Aortic aneurysms are increasingly recognized as an immune-mediated disease with a strong genetic component, where chronic inflammation plays a pivotal role in driving pathological remodeling and weakening of the aortic wall.^[6] Inflammatory signaling pathways, such as those initiated by the IL6R (Interleukin-6 Receptor), can directly influence the activity of key proteolytic enzymes like MMP9, thereby linking inflammatory responses to the degradation of the extracellular matrix.^[6] This inflammatory environment promotes increased angiogenesis, or the formation of new blood vessels, at the site of abdominal aortic aneurysms, which is further associated with the overexpression of proangiogenic factors.^[22] This neovascularization contributes to the overall inflammatory milieu and exacerbates the structural compromise of the aortic wall.

The complex interplay of immune cells and their secreted inflammatory mediators creates a self-perpetuating cycle of inflammation and tissue destruction. The integration of specific signaling pathways, such as those involving IL6R, into broader molecular networks highlights the systems-level nature of aneurysm pathogenesis.^[6]These intricate network interactions suggest that therapeutic strategies targeting specific inflammatory pathways or immune cell activation could be crucial in mitigating aneurysm progression and rupture.

Genetic Risk Stratification and Prognostic Insights

Genetic studies play a crucial role in understanding the etiology and predicting the progression of aortic aneurysm. Meta-analyses of genome-wide association studies (GWAS) have identified multiple disease-specific risk loci for abdominal aortic aneurysm (AAA), including variants inLRP1, DAB2IP, and a sequence variant associated with SORT1 on 1p13.3.^[6]These genetic insights contribute significantly to unraveling the molecular mechanisms underlying aneurysm formation and expansion, which can inform future therapeutic targets. The application of polygenic risk scores (PRS) using logistic regression models allows for the estimation of odds ratios, integrating these genetic markers with clinical factors like age, sex, and ancestry to refine individual risk assessment.^[25] Furthermore, genetic findings offer substantial prognostic value by identifying individuals at higher risk for adverse outcomes. Aortic calcification, which is influenced by genes such as HDAC9, serves as an important independent predictor of future cardiovascular events.^[7] Specific genetic variants, like the one on 9p21, are associated not only with AAA but also with myocardial infarction and intracranial aneurysms, highlighting their broad prognostic significance for vascular health.^[1] The identification of susceptibility loci for thoracic aortic aneurysms (TAA) and aortic dissections, such as those spanning FBN1 at 15q21.1, and specific SNPs like rs1036477 and rs2118181 with notable odds ratios, further enhances the predictive power of genetic markers for disease development and complications.^[3]

Integrated Clinical Applications and Monitoring Strategies

The clinical management of aortic aneurysm benefits significantly from early diagnostic utility and tailored monitoring strategies. Ultrasonography screening is a well-established clinical application for detecting AAA.^[6] with guidelines from bodies like the US Preventive Services Task Force recommending its use.^[25] However, the prevalence of late diagnoses suggests an underutilization of current screening protocols, underscoring the need for more effective risk stratification.^[25] Integrating genetic information, particularly polygenic risk scores that account for family history and smoking status, can enhance risk assessment beyond traditional clinical parameters, allowing for more targeted screening and preventive interventions.^[25] Understanding the genetic architecture, including pathways like Interleukin-6 receptor pathways, can guide the selection of personalized treatment strategies.^[6] For instance, individuals with specific genetic variants linked to ascending aortic aneurysms or aortic dissection may benefit from earlier or more intensive surveillance, influencing the timing of surgical intervention.^[3] Monitoring strategies are also informed by the natural history of associated conditions, such as the progression of common iliac artery aneurysms in patients with AAA, providing a comprehensive approach to patient care and long-term management.^[25]

Overlapping Vascular Phenotypes and Comorbidities

Aortic aneurysm often presents as part of a broader spectrum of vascular disease, characterized by shared genetic predispositions and clinical comorbidities. Research indicates shared genetic risk factors among intracranial, abdominal, and thoracic aneurysms, explaining the co-occurrence of these conditions.^[5]A notable example is the variant on 9p21, which associates with myocardial infarction, AAA, and intracranial aneurysm, demonstrating a common genetic vulnerability across different vascular beds.^[1] This genetic overlap contributes to the observed high frequency of thoracic aneurysms in patients diagnosed with AAA, and an increased incidence of femoral and popliteal artery aneurysms in this population.^[5]Patients with aortic aneurysm frequently exhibit significant comorbidities that influence their overall health and prognosis. These often include higher rates of statin therapy, diabetes mellitus, and a history of smoking compared to control populations.^[25]The presence of these overlapping phenotypes and comorbid conditions necessitates a holistic clinical assessment and management plan. By leveraging genetic insights into shared disease pathways, clinicians can more effectively identify individuals at elevated risk for multiple vascular pathologies and develop integrated prevention strategies that address the full spectrum of their cardiovascular health.^[25]

Key Variants

RS ID	Gene	Related Traits
rs1333047 rs10757279 rs4977575	CDKN2B-AS1	pulse pressure hypertension large artery stroke hemorrhoid non-high density lipoprotein cholesterol
rs12857403 rs12875918 rs9510086	LINC00540 - FTH1P7	aortic aneurysm aneurysm Abdominal Aortic Aneurysm
rs4936098	ADAMTS8, ZBTB44-DT	pulse pressure , alcohol drinking systolic blood pressure Abdominal Aortic Aneurysm hypertension aortic aneurysm
rs11172113	LRP1	migraine disorder migraine without aura, susceptibility to, 4 FEV/FVC ratio, pulmonary function , smoking behavior trait FEV/FVC ratio, pulmonary function coronary artery disease
rs429358	APOE	cerebral amyloid deposition Lewy body dementia, Lewy body dementia high density lipoprotein cholesterol platelet count neuroimaging
rs964184	ZPR1	very long-chain saturated fatty acid coronary artery calcification vitamin K total cholesterol triglyceride
rs10455872	LPA	myocardial infarction lipoprotein-associated phospholipase A(2) response to statin lipoprotein A parental longevity
rs3827066	ZNF335	coronary artery disease Abdominal Aortic Aneurysm coronary atherosclerosis occlusion precerebral artery aneurysm
rs1106370	SPSB1 - LINC02606	Inguinal hernia Abdominal Aortic Aneurysm aortic aneurysm aneurysm
rs10736085	PLCE1	aortic aneurysm aneurysm

Frequently Asked Questions About Aortic Aneurysm

These questions address the most important and specific aspects of aortic aneurysm based on current genetic research.

---

1. My dad had an aneurysm; will I get one too?

Having a first-degree relative like your dad with an aortic aneurysm significantly increases your risk, by about 2 to 11 times. This is because aortic aneurysms, especially abdominal ones (AAA), have a high heritability, meaning genetics play a strong role in up to 70% of cases. It’s important to discuss this family history with your doctor.

2. Why did my sibling get an aneurysm, but I didn’t?

Even with a shared family history, genetic predispositions can manifest differently. While your family might carry certain genetic variants associated with aneurysm risk, like those in theLRP1 or DAB2IP genes for AAA, or FBN1 for TAA, other genetic or environmental factors can influence who actually develops the condition. It’s not a guarantee, even with a strong genetic link.

3. Can I prevent an aneurysm if it runs in my family?

While you can’t change your genetic predisposition, understanding your family history is crucial for prevention. Knowing your risk allows for targeted screening and early detection, which are vital for timely management. Lifestyle factors also play a role, and your doctor can help you develop preventive strategies.

4. I’m not European; does my background change my aneurysm risk?

Yes, your ancestry can influence your risk. Much of the genetic research on aortic aneurysms has focused on people of European descent. This means that genetic variants identified might not be as common or have the same effect in non-European populations, and certain aneurysm types, like abdominal aortic aneurysms, are known to disproportionately affect white populations.

5. Should I get screened if aneurysms run in my family?

Yes, absolutely. Given the strong genetic component and significant risk associated with a family history, early detection through screening is very important. For abdominal aortic aneurysms (AAA) in particular, screening programs exist to identify individuals at risk, allowing for surveillance or timely repair before a life-threatening event occurs.

6. What would a DNA test tell me about my aneurysm risk?

A DNA test could identify specific genetic variants linked to aneurysm susceptibility. For example, variants in genes likeLRP1 and DAB2IPare associated with abdominal aortic aneurysm, while variants inFBN1 are linked to thoracic aortic aneurysms. These findings could help your doctor better assess your personal risk and guide screening or preventive measures.

7. My family has heart problems; is that linked to aneurysms?

Yes, there are shared genetic risk factors between aneurysms and other cardiovascular conditions. For instance, a specific genetic variant on chromosome 9p21 is associated with myocardial infarction (heart attack), abdominal aortic aneurysm, and intracranial aneurysm. Additionally, aortic calcification, which is related to heart health, is a strong predictor of future cardiovascular events.

8. Can a healthy lifestyle overcome my family’s aneurysm history?

While genetics are a major factor, contributing up to 70% to the heritability of conditions like abdominal aortic aneurysm, environmental factors also play a role. A healthy lifestyle can help manage overall cardiovascular health and potentially mitigate some risks. However, given a strong family history, it’s crucial to combine lifestyle efforts with medical surveillance and advice from your doctor.

9. Why do white people seem to get AAA more often?

Abdominal aortic aneurysms (AAA) are indeed observed to disproportionately affect white populations. The exact reasons are complex, but genetic research has largely focused on individuals of European ancestry. This could mean that the specific genetic risk factors identified are more prevalent or have different effects within this group compared to other ethnic backgrounds.

10. Can I pass aneurysm risk to my kids if I don’t have one?

Yes, it’s possible. Aortic aneurysms have a high heritability, meaning genetic factors are strongly involved in their development. Even if you don’t develop an aneurysm yourself, you could carry genetic variants associated with increased risk and pass those on to your children, making them more susceptible. This is why understanding family history is so important.

---

This FAQ was automatically generated based on current genetic research and may be updated as new information becomes available.

Disclaimer: This information is for educational purposes only and should not be used as a substitute for professional medical advice. Always consult with a healthcare provider for personalized medical guidance.

References

[1] Bown, M. J. “Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1.”Am J Hum Genet, 2011.

[2] Gretarsdottir, S., Baas, A. F., Thorleifsson, G., Holm, H., den Heijer, M., de Vries, J. P., . & Consortium, I. A. A. (2010). Genome-wide association study identifies a sequence variant within the DAB2IP gene conferring susceptibility to abdominal aortic aneurysm.Nature Genetics, 42(8), 692-697.

[3] LeMaire, S. A., et al. “Genome-wide association study identifies a susceptibility locus for thoracic aortic aneurysms and aortic dissections spanning FBN1 at 15q21.1.” Nature Genetics, vol. 43, no. 10, 2011, pp. 996–1000.

[4] Helgadottir, A., et al. “The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm.”Nature Genetics, vol. 40, no. 2, 2008, pp. 217-224.

[5] van ‘t Hof, F. N., et al. “Shared Genetic Risk Factors of Intracranial, Abdominal, and Thoracic Aneurysms.” J Am Heart Assoc, 2016.

[6] Jones, G. T., et al. “Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci.”Circ Res, vol. 120, 2017, pp. 344–353.

[7] Malhotra, R., et al. “HDAC9 is implicated in atherosclerotic aortic calcification and affects vascular smooth muscle cell phenotype.”Nature Genetics, vol. 51, no. 12, 2019, pp. 1620–1627.

[8] Hannou, S. A., et al. “Functional Genomics of the CDKN2A/B Locus in Cardiovascular and Metabolic Disease: What Have We.”Trends in Endocrinology & Metabolism, vol. 26, no. 4, Apr. 2015.

[9] Wain, L. V., et al. “Genome-Wide Association Study Identifies Six New Loci Influencing Pulse Pressure and Mean Arterial Pressure.”Nature Genetics, vol. 43, no. 10, Sep. 2011, pp. 1005-1011.

[10] Kim, D. S., et al. “PLTP Activity Inversely Correlates with CAAD: Effects of PON1 Enzyme Activity and Genetic Variants on PLTP Activity.” Journal of Lipid Research, vol. 54, no. 2, Feb. 2013, pp. 540-547.

[11] Eriksson, P., et al. “A population-based case-control study of the familial risk of abdominal aortic aneurysm.”Journal of Vascular Surgery, vol. 49, no. 1, 2009, pp. 47-50.

[12] Guo, D. C., et al. “Genetic variants in LRP1 and ULK4 are associated with aortic disease.”American Journal of Human Genetics, vol. 99, no. 2, 2016, pp. 386–396.

[13] Biros, E., et al. “Differential gene expression in human abdominal aortic aneurysm and oncotarget.”Oncotarget, vol. 5, no. 14, 2014.

[14] Pahl, M. C., et al. “Transcriptional (ChIP-Chip) analysis of ELF1, ETS2, RUNX1 and STAT5 in human abdominal aortic aneurysm.”International Journal of Molecular Sciences, vol. 16, no. 5, 2015, pp. 11229-11246.

[15] Hong, E. P., et al. “Genomic Variations in Susceptibility to Intracranial Aneurysm in the Korean Population.”J Clin Med, 2019.

[16] Maki, J. M., et al. “Inactivation of the lysyl oxidase gene Lox leads to aortic aneurysms, cardiovascular dysfunction, and perinatal death in mice.”Circulation, vol. 106, no. 20, 2002, pp. 2503-2509.

[17] Kuivaniemi, H., et al. “Aortic aneurysms: an immune disease with a strong genetic component.”Circulation, vol. 102, no. 21, 2000, pp. 2551-2556.

[18] Penn, D. L., et al. “The role of vascular remodeling and inflammation in the pathogenesis of intracranial aneurysms.” Journal of Clinical Neuroscience, vol. 21, no. 1, 2014, pp. 28-32.

[19] Loeys, B. L., et al. “Aneurysm syndromes caused by mutations in the TGF-beta receptor.”New England Journal of Medicine, vol. 355, no. 8, 2006, pp. 788-798.

[20] Milewicz, D. M., et al. “Genetic variants promoting smooth muscle cell proliferation can result in diffuse and diverse vascular diseases: Evidence for a hyperplastic vasculomyopathy.”Genetics in Medicine, vol. 12, no. 4, 2010, pp. 196-203.

[21] Norman, P. E., and J. T. Powell. “Site specificity of aneurysmal disease.”Circulation, vol. 121, no. 4, 2010, pp. 560-568.

[22] Choke, E., et al. “Abdominal aortic aneurysm rupture is associated with increased medial neovascularization and overexpression of proangiogenic factors.”Arterioscler Thromb Vasc Biol, 2007.

[23] Levy, D., et al. “Framingham Heart Study 100K Project: genome-wide associations for blood pressure and arterial stiffness.”BMC Med Genet, 2007.

[24] Muratoglu, S. C., et al. “LRP1 protects the vasculature by regulating levels of connective tissue growth factor and HtrA1.” Arterioscler Thromb Vasc Biol, 2014.

[25] Klarin, D., et al. “Genetic Architecture of Abdominal Aortic Aneurysm in the Million Veteran Program.”Circulation.