Vascular Genetics: Presentations, Testing, and Prognostics

Aday, Aaron W.; Kreykes, Sarah; Fanola, Christina

doi:10.1007/s11936-018-0703-2

Cited by 8 publications

(6 citation statements)

References 84 publications

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“…The clinical translation of genetic research has been a topic of interest for the last decades. For rare diseases like Marfan or Ehlers-Danlos syndrome, genetic clinical utility has been proven and applied 28 , but for more common complex diseases like AAA, the interpretation and translation of large-scale genetic studies is challenging at best 29 . GWAS-derived association studies were mainly investigated in intracranial and abdominal aneurysm patients 30–35 .…”

Section: Discussionmentioning

confidence: 99%

Polygenic Susceptibility of Aortic Aneurysms Associates to the Diameter of the Aneurysm Sac: the Aneurysm-Express Biobank Cohort

Laarhoven

Setten

Herwaarden

et al. 2019

Sci Rep

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Recent genome-wide association studies (GWAS) have discovered ten genetic risk variants for abdominal aortic aneurysms (AAA). To what extent these genetic variants contribute to the pathology of aneurysms is yet unknown. The present study aims to investigate whether genetic risk variants are associated with three clinical features: diameter of aneurysm sac, type of artery and aneurysm related-symptoms in aortic and peripheral aneurysm patients. Aneurysm tissue of 415 patients included in the Aneurysm-Express biobank was used. A best-fit polygenic risk score (PRS) based on previous GWAS effect estimates was modeled for each clinical phenotype. The best-fit PRS (including 272 variants at PT = 0.01015) showed a significant correlation with aneurysm diameter (R2 = 0.019, p = 0.001). No polygenic association was found with clinical symptoms or artery type. In addition, the ten genome-wide significant risk variants for AAA were tested individually, but no associations were observed with any of the clinical phenotypes. All models were corrected for confounders and data was normalized. In conclusion, a weighted PRS of AAA susceptibility explained 1.9% of the phenotypic variation (p = 0.001) in diameter in aneurysm patients. Given our limited sample size, future biobank collaborations need to confirm a potential causal role of susceptibility variants on aneurysmal disease initiation and progression.

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Section: Discussionmentioning

confidence: 99%

Polygenic Susceptibility of Aortic Aneurysms Associates to the Diameter of the Aneurysm Sac: the Aneurysm-Express Biobank Cohort

Laarhoven

Setten

Herwaarden

et al. 2019

Sci Rep

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show abstract

“…The clinical translation of genetic research has been a topic of interest for the last decades. For rare diseases like Marfan or Ehlers-Danlos syndrome, genetic clinical utility has been proven and applied, [27] but for more common complex diseases like AAA, the interpretation and translation of large-scale genetic studies is challenging at best. [28] GWAS-derived association studies were mainly investigated in intracranial and abdominal aneurysm patients.…”

Section: Discussionmentioning

confidence: 99%

Polygenic Susceptibility of Aortic Aneurysms Associates to the Diameter of the Aneurysm Sac: the Aneurysm-Express Biobank Cohort

Laarhoven

Setten

Herwaarden

et al. 2019

Preprint

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Purpose: Abdominal aortic aneurysms (AAA) have a multifactorial pathology with both genetic and environmental risk factors. Recent genome-wide association studies (GWAS) have discovered ten genetic risk loci for AAA. To what extent these genetic loci contribute to the aneurysm pathology is yet unknown. This study aims to investigate whether genetic risk variants are associated with three clinical features: diameter of aneurysm sac, type of artery and symptoms.Methods: We used aneurysm tissue from 415 patients included within the Aneurysm-Express biobank. A best fit polygenic risk score (PRS) based on previous GWAS effect size estimates was modeled for each clinical parameter by comparing model predictions across different p-value thresholds. Next, the established 10 risk variants for AAA were tested individually for association with selected clinical phenotypes. Models were corrected for age, sex, ancestral background, smoking status and diameter of the aneurysm sac or artery type if applicable, and data was normalized.Results: The best fit PRS (including 272 SNPs with P T =0.01015) showed a significant correlation with diameter of the aneurysm sac (R 2 = 0.019, p = 0.001). No association was found with clinical symptoms or type of artery. Individual variant analysis showed no clear associations with any of the clinical features.Conclusions: Within the Aneurysm-Express Biobank Study, a weighted polygenic score of AAA susceptibility explained 1.9% of the phenotypic variation (p = 0.001) in aneurysm diameter. Individual risk variant analysis showed no clear associations. Given our limited sample size, future biobank collaborations need to confirm a potential causal role of individual SNPs on the pathology of aneurysms.

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“…With increasing use and availability of genetic testing and genome-wide association studies (GWAS), it is estimated that hereditary factors play an important role in the etiology of thoracic aortic aneurysms and dissections (TAAD). In contrast to rare pathogenic variants that impair the connective tissue structure of the vascular system and cause inherited disorders such as Marfan, Ehlers-Danlos or Loeys-Dietz syndrome, common genetic variants also occur in the general population, such as single-nucleotide variations (SNV) or genomic copy number variations (CNV), which slightly increase the risk for TAAD [3,4].…”

Section: Introductionmentioning

confidence: 99%

Genetic Variation in LRP1 Associates with Stanford Type B Aortic Dissection Risk and Clinical Outcome

Erhart

Grond‐Ginsbach

Qiao

et al. 2022

JCDD

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Genetic variation in LRP1 (low-density lipoprotein receptor-related protein 1) was reported to be associated with thoracic aortic dissections and aneurysms. The aims of this study were to confirm this association in a prospective single-center patient cohort of patients with acute Stanford type B aortic dissections (STBAD) and to assess the impact of LRP1 variation on clinical outcome. The single nucleotide variation (SNV) rs11172113 within the LRP1 gene was genotyped in 113 STBAD patients and 768 healthy control subjects from the same population. The T-allele of rs11172113 was more common in STBAD patients as compared to the reference group (72.6% vs. 59.6%) and confirmed to be an independent risk factor for STBAD (p = 0.002) after sex and age adjustment in a logistic regression model analyzing diabetes, smoking and hypertension as additional risk factors. Analysis of clinical follow-up (median follow-up 2.0 years) revealed that patients with the T-allele were more likely to suffer aorta-related complications (T-allele 75.6% vs. 63.8%; p = 0.022). In this study sample of STBAD patients, variation in LRP1 was an independent risk factor for STBAD and affected clinical outcome.

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Vascular Genetics: Presentations, Testing, and Prognostics

Cited by 8 publications

References 84 publications

Polygenic Susceptibility of Aortic Aneurysms Associates to the Diameter of the Aneurysm Sac: the Aneurysm-Express Biobank Cohort

Polygenic Susceptibility of Aortic Aneurysms Associates to the Diameter of the Aneurysm Sac: the Aneurysm-Express Biobank Cohort

Polygenic Susceptibility of Aortic Aneurysms Associates to the Diameter of the Aneurysm Sac: the Aneurysm-Express Biobank Cohort

Genetic Variation in LRP1 Associates with Stanford Type B Aortic Dissection Risk and Clinical Outcome

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