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

By Constance JHCM van Laarhoven, Jessica van Setten, Joost A van Herwaarden, Dominique P.V. de Kleijn, Gerard Pasterkamp, Gert J de Borst, Sander W. van der Laan

Posted 15 May 2019
bioRxiv DOI: 10.1101/636795 (published DOI: 10.1038/s41598-019-56230-3)

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 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. 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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