Abstract
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.
Highlights
In the past decade, genome-wide association studies (GWAS) have uncovered ten common genetic variants, i.e. single-nucleotide polymorphisms (SNPs), associated to abdominal aortic aneurysms (AAA) susceptibility[6,7,8,9,10,11,12]
We investigated whether AAA susceptibility variants in aggregate are associated with three clinical phenotypes within the Aneurysm-Express biobank study[17]
In order to verify the predictive value of the polygenic risk score (PRS) of the AAA-GWAS, we modeled a PRS of summary statistics of the attention deficit hyperactivity disorder (ADHD) GWAS unrelated to AAA24, and tested this additional polygenic score for association with the selected clinical parameters in our study cohort
Summary
Genome-wide association studies (GWAS) have uncovered ten common genetic variants, i.e. single-nucleotide polymorphisms (SNPs), associated to AAA susceptibility[6,7,8,9,10,11,12]. We investigated whether AAA susceptibility variants in aggregate are associated with three clinical phenotypes (maximum diameter of aneurysm sac, aneurysm related symptoms, and type of artery) within the Aneurysm-Express biobank study[17]. These phenotypes encompass interventions and are clinically relevant. Our results show that higher PRS associates to larger aneurysm diameter, but no association was found with clinical symptoms or type of artery
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
