Shared genetic risk factors of intracranial, abdominal, and thoracic aneurysms

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dc.contributor.authorVan 't Hof, Femke N. G.en_ZA
dc.contributor.authorRuigrok, Ynte M.en_ZA
dc.contributor.authorLee, Cue Hyunkyuen_ZA
dc.contributor.authorRipke, Stephanen_ZA
dc.contributor.authorAnderson, Graigen_ZA
dc.contributor.authorDe Andrade, Marizaen_ZA
dc.contributor.authorTromp, Gerarden_ZA
dc.date.accessioned2017-07-12T12:09:18Z
dc.date.available2017-07-12T12:09:18Z
dc.date.issued2016-07-14
dc.descriptionCITATION: Van 't Hof, F. N. G. et al. 2016. Shared genetic risk factors of intracranial, abdominal, and thoracic aneurysms. Journal of the American Heart Association, 5:e002603, doi:10.1161/JAHA.115.002603.
dc.descriptionThe original publication is available at http://jaha.ahajournals.org
dc.description.abstractBackground: Intracranial aneurysms (IAs), abdominal aortic aneurysms (AAAs), and thoracic aortic aneurysms (TAAs) all have a familial predisposition. Given that aneurysm types are known to co‐occur, we hypothesized that there may be shared genetic risk factors for IAs, AAAs, and TAAs. Methods and Results: We performed a mega‐analysis of 1000 Genomes Project‐imputed genome‐wide association study (GWAS) data of 4 previously published aneurysm cohorts: 2 IA cohorts (in total 1516 cases, 4305 controls), 1 AAA cohort (818 cases, 3004 controls), and 1 TAA cohort (760 cases, 2212 controls), and observed associations of 4 known IA, AAA, and/or TAA risk loci (9p21, 18q11, 15q21, and 2q33) with consistent effect directions in all 4 cohorts. We calculated polygenic scores based on IA‐, AAA‐, and TAA‐associated SNPs and tested these scores for association to case‐control status in the other aneurysm cohorts; this revealed no shared polygenic effects. Similarly, linkage disequilibrium–score regression analyses did not show significant correlations between any pair of aneurysm subtypes. Last, we evaluated the evidence for 14 previously published aneurysm risk single‐nucleotide polymorphisms through collaboration in extended aneurysm cohorts, with a total of 6548 cases and 16 843 controls (IA) and 4391 cases and 37 904 controls (AAA), and found nominally significant associations for IA risk locus 18q11 near RBBP8 to AAA (odds ratio [OR]=1.11; P=4.1×10−5) and for TAA risk locus 15q21 near FBN1 to AAA (OR=1.07; P=1.1×10−3). Conclusions: Although there was no evidence for polygenic overlap between IAs, AAAs, and TAAs, we found nominally significant effects of two established risk loci for IAs and TAAs in AAAs. These two loci will require further replication.en_ZA
dc.description.urihttp://jaha.ahajournals.org/content/5/7/e002603
dc.description.versionPublisher's version
dc.format.extent20 pages
dc.identifier.citationVan 't Hof, F. N. G. et al. 2016. Shared genetic risk factors of intracranial, abdominal, and thoracic aneurysms. Journal of the American Heart Association, 5:e002603, doi:10.1161/JAHA.115.002603.
dc.identifier.issn2047-9980 (online)
dc.identifier.otherdoi:10.1161/JAHA.115.002603
dc.identifier.urihttp://hdl.handle.net/10019.1/101958
dc.language.isoen_ZAen_ZA
dc.publisherAmerican Heart Association
dc.rights.holderAuthors retain copyright
dc.subjectAneurysmsen_ZA
dc.subjectAortic aneurysmsen_ZA
dc.subjectHeart -- Diseases -- Genetic aspectsen_ZA
dc.titleShared genetic risk factors of intracranial, abdominal, and thoracic aneurysmsen_ZA
dc.typeArticleen_ZA
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