Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease (Jul 2016)
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 Fraunberg,
- Christoph 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,
- Mika Niemelä,
- Jennifer Pacheco,
- Peggy L. Peissig,
- Joanna Pera,
- Laura Rasmussen‐Torvik,
- Marylyn D. Ritchie,
- Fernando Rivadeneira,
- Andre M. van Rij,
- Regie Lyn P. Santos‐Cortez,
- Athanasios Saratzis,
- Agnieszka Slowik,
- Atsushi Takahashi,
- Gerard Tromp,
- André G. Uitterlinden,
- Shefali S. Verma,
- Sita H. Vermeulen,
- Gao T. Wang,
- Buhm Han,
- Gabriël J. E. Rinkel,
- Paul I. W. de Bakker,
- Matthew J. Bown,
- Seamus C. Harrison,
- Athanasios Saratzis,
- Ana Verissimo,
- Benjamin J. Wright,
- Suzannah Bumpstead,
- Annette F. Baas,
- Solveig Gretarsdottir,
- Stephen A. Badger,
- Anne H. Child,
- Rachel E. Clough,
- Gillian Cockerill,
- Hany Hafez,
- D. Julian A. Scott,
- Simon Futers,
- Soroush Sohrabi,
- Alberto Smith,
- Matthew M. Thompson,
- Frank M. van Bockxmeer,
- Stefan E. Matthiasson,
- Gudmar Thorleifsson,
- Unnur Thorsteinsdottir,
- Jan D. Blankensteijn,
- Joep A. W. Teijink,
- Cisca Wijmenga,
- Jacqueline de Graaf,
- Lambertus A. Kiemeney,
- Jutta Palmen,
- Andrew J. Smith,
- Jes S. Lindholt,
- Declan T. Bradley,
- Matthew Waltham,
- Sarah Edkins,
- Rhian Gwilliam,
- Sarah E. Hunt,
- Simon Potter,
- Jonathan Golledge,
- Per Eriksson,
- Paul E. Norman,
- Janet T. Powell,
- Kari Stefansson,
- John R. Thompson,
- Steve E. Humphries,
- Robert D. Sayers,
- Panos Deloukas,
- Nilesh J. Samani,
- Gregory T. Jones,
- L. Victoria Phillip,
- Andre M. van Rij,
- Geraldine B. Hill,
- Michael J. A. Williams,
- Ian A. Thomson,
- Jo Krysa,
- Gerard T. Wilkins,
- Tony R. Merriman,
- Thodor M. Vasudevan,
- David R. Lewis,
- Ross D. Blair,
- Andrew A. Hill
Affiliations
- Femke N. G. van ’t Hof
- Utrecht Stroke Center, Department of Neurology and Neurosurgery, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands
- Ynte M. Ruigrok
- Utrecht Stroke Center, Department of Neurology and Neurosurgery, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands
- Cue Hyunkyu Lee
- Department of Convergence Medicine, University of Ulsan College of Medicine and Asan Institute for Life Sciences Asan Medical Center, Seoul, Korea
- Stephan Ripke
- Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA
- Graig Anderson
- The George Institute for International Health, University of Sydney, Australia
- Mariza de Andrade
- Mayo Clinic, Rochester, NY
- Annette F. Baas
- Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands
- Jan D. Blankensteijn
- Department of Vascular Surgery, VU Medical Center, Amsterdam, The Netherlands
- Erwin P. Böttinger
- Icahn School of Medicine Mount Sinai, The Charles Bronfman Institute for Personalized Medicine, New York, NY
- Matthew J. Bown
- Department of Cardiovascular Sciences and the NIHR Leicester Cardiovascular Biomedical Research Unit, University of Leicester, United Kingdom
- Joseph Broderick
- Department of Neurology, University of Cincinnati School of Medicine, Cincinnati, OH
- Philippe Bijlenga
- Hôpitaux Universitaire de Genève et Faculté de médecine de Genève, Geneva, Switzerland
- David S. Carrell
- Group Health Research Institute, Seattle, WA
- Dana C. Crawford
- Department of Epidemiology and Biostatistics, Institute for Computational Biology, Case Western Reserve University, Cleveland, OH
- David R. Crosslin
- Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA
- Christian Ebeling
- Fraunhofer Institut Algorithmen und Wissenschaftliches Rechnen, Sankt Augustin, Germany
- Johan G. Eriksson
- Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland
- Myriam Fornage
- Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX
- Tatiana Foroud
- Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN
- Mikael von und zu Fraunberg
- Neurosurgery of NeuroCenter, Kuopio University Hospital, Kuopio, Finland
- Christoph M. Friedrich
- Department of Computer Science, University of Applied Science and Arts, Dortmund, Germany
- Emília I. Gaál
- Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland
- Omri Gottesman
- Icahn School of Medicine Mount Sinai, The Charles Bronfman Institute for Personalized Medicine, New York, NY
- Dong‐Chuan Guo
- Department of Internal Medicine, The University of Texas Medical School at Houston, TX
- Seamus C. Harrison
- Department of Cardiovascular Science, University of Leicester, United Kingdom
- Juha Hernesniemi
- Department of Neurosurgery, Helsinki University Central Hospital, Helsinki, Finland
- Albert Hofman
- Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
- Ituro Inoue
- Division of Human Genetics, National Institute of Genetics, Mishima, Japan
- Juha E. Jääskeläinen
- Neurosurgery of NeuroCenter, Kuopio University Hospital, Kuopio, Finland
- Gregory T. Jones
- Surgery Department, University of Otago, Dunedin, New Zealand
- Lambertus A. L. M. Kiemeney
- Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands
- Riku Kivisaari
- Department of Neurosurgery, Helsinki University Central Hospital, Helsinki, Finland
- Nerissa Ko
- Department of Neurology, University of California, San Francisco, CA
- Seppo Koskinen
- Department of Health, Functional Capacity and Welfare, National Institute for Health and Welfare, Helsinki, Finland
- Michiaki Kubo
- Center for Integrative Medical Sciences, RIKEN, Kanagawa, Japan
- Iftikhar J. Kullo
- Mayo Clinic, Rochester, NY
- Helena Kuivaniemi
- Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands
- Mitja I. Kurki
- Neurosurgery of NeuroCenter, Kuopio University Hospital, Kuopio, Finland
- Aki Laakso
- Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland
- Dongbing Lai
- Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN
- Suzanne M. Leal
- Center for Statistical Genetics, Baylor College of Medicine, Houston, TX
- Hanna Lehto
- Department of Neurosurgery, Helsinki University Central Hospital, Helsinki, Finland
- Scott A. LeMaire
- Michael E. DeBakey Department of Surgery, Baylor College of Medicine and the Texas Heart Institute, Houston, TX
- Siew‐Kee Low
- Center for Integrative Medical Sciences, RIKEN, Kanagawa, Japan
- Jennifer Malinowski
- Center for Human Genetics Research, Vanderbilt University, Nashville, TN
- Catherine A. McCarty
- Research Division, Essentia Institute of Rural Health, Duluth, MN
- Dianna M. Milewicz
- Department of Internal Medicine, The University of Texas Medical School at Houston, TX
- Thomas H. Mosley
- Department of Medicine, University of Mississippi Medical Center, Jackson, MS
- Yusuke Nakamura
- Section of Hematology and Oncology, Department of Medicine, University of Chicago, IL
- Hirofumi Nakaoka
- Division of Human Genetics, National Institute of Genetics, Mishima, Japan
- Mika Niemelä
- Department of Neurosurgery, Helsinki University Central Hospital, Helsinki, Finland
- Jennifer Pacheco
- Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL
- Peggy L. Peissig
- Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, WI
- Joanna Pera
- Department of Neurology, Jagiellonian University, Krakow, Poland
- Laura Rasmussen‐Torvik
- Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL
- Marylyn D. Ritchie
- Center for Systems Genomics, The Pennsylvania State University, Pennsylvania, PA
- Fernando Rivadeneira
- Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
- Andre M. van Rij
- Surgery Department, University of Otago, Dunedin, New Zealand
- Regie Lyn P. Santos‐Cortez
- Center for Statistical Genetics, Baylor College of Medicine, Houston, TX
- Athanasios Saratzis
- Department of Cardiovascular Sciences and the NIHR Leicester Cardiovascular Biomedical Research Unit, University of Leicester, United Kingdom
- Agnieszka Slowik
- Department of Neurology, Jagiellonian University, Krakow, Poland
- Atsushi Takahashi
- Center for Integrative Medical Sciences, RIKEN, Kanagawa, Japan
- Gerard Tromp
- The Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA
- André G. Uitterlinden
- Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
- Shefali S. Verma
- Center for Systems Genomics, The Pennsylvania State University, Pennsylvania, PA
- Sita H. Vermeulen
- Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands
- Gao T. Wang
- Center for Statistical Genetics, Baylor College of Medicine, Houston, TX
- Buhm Han
- Department of Convergence Medicine, University of Ulsan College of Medicine and Asan Institute for Life Sciences Asan Medical Center, Seoul, Korea
- Gabriël J. E. Rinkel
- Utrecht Stroke Center, Department of Neurology and Neurosurgery, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands
- Paul I. W. de Bakker
- Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
- Matthew J. Bown
- Seamus C. Harrison
- Athanasios Saratzis
- Ana Verissimo
- Benjamin J. Wright
- Suzannah Bumpstead
- Annette F. Baas
- Solveig Gretarsdottir
- Stephen A. Badger
- Anne H. Child
- Rachel E. Clough
- Gillian Cockerill
- Hany Hafez
- D. Julian A. Scott
- Simon Futers
- Soroush Sohrabi
- Alberto Smith
- Matthew M. Thompson
- Frank M. van Bockxmeer
- Stefan E. Matthiasson
- Gudmar Thorleifsson
- Unnur Thorsteinsdottir
- Jan D. Blankensteijn
- Joep A. W. Teijink
- Cisca Wijmenga
- Jacqueline de Graaf
- Lambertus A. Kiemeney
- Jutta Palmen
- Andrew J. Smith
- Jes S. Lindholt
- Declan T. Bradley
- Matthew Waltham
- Sarah Edkins
- Rhian Gwilliam
- Sarah E. Hunt
- Simon Potter
- Jonathan Golledge
- Per Eriksson
- Paul E. Norman
- Janet T. Powell
- Kari Stefansson
- John R. Thompson
- Steve E. Humphries
- Robert D. Sayers
- Panos Deloukas
- Nilesh J. Samani
- Gregory T. Jones
- L. Victoria Phillip
- Andre M. van Rij
- Geraldine B. Hill
- Michael J. A. Williams
- Ian A. Thomson
- Jo Krysa
- Gerard T. Wilkins
- Tony R. Merriman
- Thodor M. Vasudevan
- David R. Lewis
- Ross D. Blair
- Andrew A. Hill
- DOI
- https://doi.org/10.1161/JAHA.115.002603
- Journal volume & issue
-
Vol. 5,
no. 7
Abstract
BackgroundIntracranial 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 ResultsWe 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). ConclusionsAlthough 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.
Keywords
- abdominal aortic aneurysm
- genome wide association study
- intracranial aneurysm
- thoracic aortic aneurysm
