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dc.contributor.authorAshvetiya, Tamara
dc.contributor.authorFan, Sherry X
dc.contributor.authorChen, Yi-Ju
dc.contributor.authorWilliams, Charles H
dc.contributor.authorO'Connell, Jeffery R
dc.contributor.authorPerry, James A
dc.contributor.authorHong, Charles C
dc.date.accessioned2021-09-03T19:32:36Z
dc.date.available2021-09-03T19:32:36Z
dc.date.issued2021-09-01
dc.identifier.urihttp://hdl.handle.net/10713/16563
dc.description.abstractBackground: Thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA) are known to have a strong genetic component. Methods and results: In a genome-wide association study (GWAS) using the UK Biobank, we analyzed the genomes of 1,363 individuals with AAA compared to 27,260 age, ancestry, and sex-matched controls (1:20 case:control study design). A similar analysis was repeated for 435 individuals with TAA compared to 8,700 controls. Polymorphism with minor allele frequency (MAF) >0.5% were evaluated. We identified novel loci near LINC01021, ATOH8 and JAK2 genes that achieved genome-wide significance for AAA (p-value <5x10-8), in addition to three known loci. For TAA, three novel loci in CTNNA3, FRMD6 and MBP achieved genome-wide significance. There was no overlap in the genes associated with AAAs and TAAs. Additionally, we identified a linkage group of high-frequency variants (MAFs ~10%) encompassing FBN1, the causal gene for Marfan syndrome, which was associated with TAA. In FinnGen PheWeb, this FBN1 haplotype was associated with aortic dissection. Finally, we found that baseline bradycardia was associated with TAA, but not AAA. Conclusions: Our GWAS found that AAA and TAA were associated with distinct sets of genes, suggesting distinct underlying genetic architecture. We also found association between baseline bradycardia and TAA. These findings, including JAK2 association, offer plausible mechanistic and therapeutic insights. We also found a common FBN1 linkage group that is associated with TAA and aortic dissection in patients who do not have Marfan syndrome. These FBN1 variants suggest shared pathophysiology between Marfan disease and sporadic TAA.en_US
dc.description.urihttps://doi.org/10.1371/journal.pone.0247287en_US
dc.language.isoenen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.ispartofPLoS ONEen_US
dc.subject.meshAortic Aneurysm, Abdominal--geneticsen_US
dc.subject.meshAortic Aneurysm, Thoracic--geneticsen_US
dc.titleIdentification of novel genetic susceptibility loci for thoracic and abdominal aortic aneurysms via genome-wide association study using the UK Biobank Cohorten_US
dc.typeArticleen_US
dc.identifier.doi10.1371/journal.pone.0247287
dc.identifier.pmid34469433
dc.source.volume16
dc.source.issue9
dc.source.beginpagee0247287
dc.source.endpage
dc.source.countryUnited States


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