Shared Genetic Risk Factors of Intracranial, Abdominal, and Thoracic Aneurysms. Issue 7 (July 2016)

• Record Type: Journal Article
• Authors: van 't Hof, Femke N. G.; Ruigrok, Ynte M.; Lee, Cue Hyunkyu; Ripke, Stephan; Anderson, Graig; de Andrade, Mariza; Baas, Annette F.; Blankensteijn, Jan D.; Böttinger, Erwin P.; Bown, Matthew J.; Broderick, Joseph; Bijlenga, Philippe; Carrell, David S.; Crawford, Dana C.; Crosslin, David R.; Ebeling, Christian; Eriksson, Johan G.; Fornage, Myriam; Foroud, Tatiana; von und zu Fraunberg, Mikael; Friedrich, Christoph M.; Gaál, Emília I.; Gottesman, Omri; Guo, Dong‐Chuan; Harrison, Seamus C.; Hernesniemi, Juha; Hofman, Albert; Inoue, Ituro; Jääskeläinen, Juha E.; Jones, Gregory T.; Kiemeney, Lambertus A. L. M.; Kivisaari, Riku; Ko, Nerissa; Koskinen, Seppo; Kubo, Michiaki; Kullo, Iftikhar J.; Kuivaniemi, Helena; Kurki, Mitja I.; Laakso, Aki; Lai, Dongbing; Leal, Suzanne M.; Lehto, Hanna; LeMaire, Scott A.; Low, Siew‐Kee; Malinowski, Jennifer; McCarty, Catherine A.; Milewicz, Dianna M.; Mosley, Thomas H.; Nakamura, Yusuke; Nakaoka, Hirofumi; Niemelä, Mika; Pacheco, Jennifer; Peissig, Peggy L.; Pera, Joanna; Rasmussen‐Torvik, Laura; Ritchie, Marylyn D.; Rivadeneira, Fernando; van Rij, Andre M.; Santos‐Cortez, Regie Lyn P.; Saratzis, Athanasios; Slowik, Agnieszka; Takahashi, Atsushi; Tromp, Gerard; Uitterlinden, André G.; Verma, Shefali S.; Vermeulen, Sita H.; Wang, Gao T.; Han, Buhm; Rinkel, Gabriël J. E.; de Bakker, Paul I. W.;
• Other Names: Bown Matthew J. investigator.; Harrison Seamus C. investigator.; Saratzis Athanasios investigator.; Verissimo Ana investigator.; Wright Benjamin J. investigator.; Bumpstead Suzannah investigator.; Baas Annette F. investigator.; Gretarsdottir Solveig investigator.; Badger Stephen A. investigator.; Child Anne H. investigator.; Clough Rachel E. investigator.; Cockerill Gillian investigator.; Hafez Hany investigator.; Scott D. Julian A. investigator.; Futers Simon investigator.; Sohrabi Soroush investigator.; Smith Alberto investigator.; Thompson Matthew M. investigator.; van Bockxmeer Frank M. investigator.; Matthiasson Stefan E. investigator.; Thorleifsson Gudmar investigator.; Thorsteinsdottir Unnur investigator.; Blankensteijn Jan D. investigator.; Teijink Joep A. W. investigator.; Wijmenga Cisca investigator.; de Graaf Jacqueline investigator.; Kiemeney Lambertus A. investigator.; Palmen Jutta investigator.; Smith Andrew J. investigator.; Lindholt Jes S. investigator.; Bradley Declan T. investigator.; Waltham Matthew investigator.; Edkins Sarah investigator.; Gwilliam Rhian investigator.; Hunt Sarah E. investigator.; Potter Simon investigator.; Golledge Jonathan investigator.; Eriksson Per investigator.; Norman Paul E. investigator.; Powell Janet T. investigator.; Stefansson Kari investigator.; Thompson John R. investigator.; Humphries Steve E. investigator.; Sayers Robert D. investigator.; Deloukas Panos investigator.; Samani Nilesh J. investigator.; Jones Gregory T. investigator.; Phillip L. Victoria investigator.; van Rij Andre M. investigator.; Hill Geraldine B. investigator.; Williams Michael J. A. investigator.; Thomson Ian A. investigator.; Krysa Jo investigator.; Wilkins Gerard T. investigator.; Merriman Tony R. investigator.; Vasudevan Thodor M. investigator.; Lewis David R. investigator.; Blair Ross D. investigator.; Hill Andrew A. investigator.;
• Is Part Of: Journal of the American Heart Association. Volume 5:Issue 7(2016)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2016-07
• Subjects: abdominal aortic aneurysm -- genome wide association study -- intracranial aneurysm -- thoracic aortic aneurysm; Heart -- Diseases -- Periodicals; Cardiovascular system -- Diseases -- Periodicals; Cerebrovascular disease -- Periodicals; Cardiology -- Periodicals; 616.1
• DOI: 10.1161/JAHA.115.002603
• Languages: English
• ISSNs: 2047-9980

Abstract

Abstract : 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.