Polygenic Susceptibility of Aortic Aneurysms Associates to the Diameter of the Aneurysm Sac : the Aneurysm-Express Biobank Cohort
| Autor: | van der Bernard Laan, Dominique P.V. de Kleijn, Gerard Pasterkamp, Joost A. van Herwaarden, Constance J.H.C.M. van Laarhoven, Gert J. de Borst, Jessica van Setten |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Oncology Multifactorial Inheritance Epidemiology lcsh:Medicine Genome-wide association study 030204 cardiovascular system & hematology Cohort Studies 0302 clinical medicine Risk Factors Genetics research Genetic risk lcsh:Science Biological Specimen Banks Aged 80 and over 0303 health sciences Multidisciplinary Confounding Middle Aged Biobank Aortic Aneurysm 3. Good health medicine.anatomical_structure Cohort Cardiology cardiovascular system Female Artery medicine.medical_specialty Single-nucleotide polymorphism Individual risk Polymorphism Single Nucleotide Article 03 medical and health sciences Aneurysm Internal medicine medicine Humans Genetic Predisposition to Disease cardiovascular diseases General Aged 030304 developmental biology Genetic association business.industry lcsh:R medicine.disease 030104 developmental biology Sample size determination lcsh:Q business Aortic Aneurysm Abdominal Genome-Wide Association Study |
| Zdroj: | Scientific Reports, 9(1). Nature Publishing Group Scientific Reports Scientific Reports, Vol 9, Iss 1, Pp 1-7 (2019) |
| ISSN: | 2045-2322 |
| Popis: | PurposeAbdominal 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.MethodsWe 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.ResultsThe best fit PRS (including 272 SNPs with PT=0.01015) showed a significant correlation with diameter of the aneurysm sac (R2 = 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.ConclusionsWithin 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. |
| Databáze: | OpenAIRE |
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