Shared Genetic Risk Factors of Intracranial, Abdominal, and Thoracic Aneurysms

Femke N G van 't Hof, Ynte M Ruigrok, Cue Hyunkyu Lee, Stephan Ripke, Graig Anderson, Mariza de Andrade, Annette F Baas, Jan D Blankensteijn, Erwin P Böttinger, Matthew J Bown, Joseph Broderick, Philippe Bijlenga, David S Carrell, Dana C Crawford, David R Crosslin, Christian Ebeling, Johan G Eriksson, Myriam Fornage, Tatiana Foroud, Mikael von Und Zu FraunbergChristoph M Friedrich, Emília I Gaál, Omri Gottesman, Dong-Chuan Guo, Seamus C Harrison, Juha Hernesniemi, Albert Hofman, Ituro Inoue, Juha E Jääskeläinen, Gregory T Jones, Lambertus A L M Kiemeney, Riku Kivisaari, Nerissa Ko, Seppo Koskinen, Michiaki Kubo, Iftikhar J Kullo, Helena Kuivaniemi, Mitja I Kurki, Aki Laakso, Dongbing Lai, Suzanne M Leal, Hanna Lehto, Scott A LeMaire, Siew-Kee Low, Jennifer Malinowski, Catherine A McCarty, Dianna M Milewicz, Thomas H Mosley, Yusuke Nakamura, Hirofumi Nakaoka, Aneurysm Consortium; Vascular Research Consortium of New Zealand

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23 Citations (Scopus)


BACKGROUND: 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.

Original languageEnglish
Pages (from-to)1-20
JournalJournal of the American Heart Association
Issue number7
Publication statusPublished - 14 Jul 2016
Externally publishedYes


  • Journal Article

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