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; Aneurysm Consortium; Vascular Research Consortium of New Zealand; Panos Deloukas

doi:10.1161/JAHA.115.002603

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

Journal article

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Peer reviewed

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, …

Journal of the American Heart Association, Vol.5(7), pp.e002603-e002603

01/01/2016

DOI: https://doi.org/10.1161/JAHA.115.002603

PMCID: PMC5015357

PMID: 27418160

Abstract

Aged

Aortic Aneurysm, Abdominal - genetics

Aortic Aneurysm, Thoracic - genetics

Case-Control Studies

Cohort Studies

Female

Genetic Predisposition to Disease

Genome-Wide Association Study

Humans

Intracranial Aneurysm - genetics

Linkage Disequilibrium

Male

Middle Aged

Odds Ratio

Polymorphism, Single Nucleotide

Risk Factors

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. 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)). 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.

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Title: Shared Genetic Risk Factors of Intracranial, Abdominal, and Thoracic Aneurysms
Creators - without role: Femke N G van 't Hof - University Medical Center Utrecht
Ynte M Ruigrok - University Medical Center Utrecht
Cue Hyunkyu Lee - University of Ulsan
Stephan Ripke - Charité - Universitätsmedizin Berlin
Graig Anderson - University of Sydney
Mariza de Andrade - Mayo Clinic, Rochester, NY
Annette F Baas - University Medical Center Utrecht
Jan D Blankensteijn - Department of Vascular Surgery, VU Medical Center, Amsterdam, The Netherlands
Erwin P Böttinger - Mount Saint Vincent University
Matthew J Bown - University of Leicester
Joseph Broderick - University of Cincinnati
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 - Case Western Reserve University
David R Crosslin - University of Washington
Christian Ebeling - Fraunhofer Institut Algorithmen und Wissenschaftliches Rechnen, Sankt Augustin, Germany
Johan G Eriksson - Helsinki University Hospital
Myriam Fornage - Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX
Tatiana Foroud - Indiana University
Mikael von Und Zu Fraunberg - Kuopio University Hospital
Christoph M Friedrich - Department of Computer Science, University of Applied Science and Arts, Dortmund, Germany
Emília I Gaál - University of Helsinki
Omri Gottesman - Mount Saint Vincent University
Dong-Chuan Guo - Department of Internal Medicine, The University of Texas Medical School at Houston, TX
Seamus C Harrison - University of Leicester
Juha Hernesniemi - Department of Neurosurgery, Helsinki University Central Hospital, Helsinki, Finland
Albert Hofman - Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
Ituro Inoue - National Institute of Genetics
Juha E Jääskeläinen - Kuopio University Hospital
Gregory T Jones - University of Otago
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 - University of California, San Francisco
Seppo Koskinen - Department of Health, Functional Capacity and Welfare, National Institute for Health and Welfare, Helsinki, Finland
Michiaki Kubo - RIKEN
Iftikhar J Kullo - Winneshiek Medical Center
Helena Kuivaniemi - Stellenbosch University
Mitja I Kurki - Kuopio University Hospital
Aki Laakso - Genomics
Dongbing Lai - Indiana University
Suzanne M Leal - Baylor College of Medicine
Hanna Lehto - Department of Neurosurgery, Helsinki University Central Hospital, Helsinki, Finland
Scott A LeMaire - Baylor College of Medicine
Siew-Kee Low - RIKEN
Jennifer Malinowski - Vanderbilt University
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 - University of Mississippi Medical Center
Yusuke Nakamura - University of Chicago
Hirofumi Nakaoka - National Institute of Genetics
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
Joanna Pera - Jagiellonian University
Laura Rasmussen-Torvik - Northwestern University
Marylyn D Ritchie - Pennsylvania State University
Fernando Rivadeneira - Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
Andre M van Rij - University of Otago
Regie Lyn P Santos-Cortez - Baylor College of Medicine
Athanasios Saratzis - University of Leicester
Agnieszka Slowik - Jagiellonian University
Atsushi Takahashi - RIKEN
Gerard Tromp - Stellenbosch University
André G Uitterlinden - Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
Shefali S Verma - Pennsylvania State University
Sita H Vermeulen - Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands
Gao T Wang - Baylor College of Medicine
Buhm Han - University of Ulsan
Gabriël J E Rinkel - University Medical Center Utrecht
Paul I W de Bakker - University Medical Center Utrecht
Aneurysm Consortium; Vascular Research Consortium of New Zealand
Panos Deloukas - King Abdulaziz University
Publication Details: Journal of the American Heart Association, Vol.5(7), pp.e002603-e002603
Grant note: UL1 RR024975 / NCRR NIH HHS HHSN268201100007C / NHLBI NIH HHS U01 HG004402 / NHGRI NIH HHS FS/11/16/28696 / British Heart Foundation P50 HL083794 / NHLBI NIH HHS HHSN268201100012C / NHLBI NIH HHS K08 HL080085 / NHLBI NIH HHS U01 HG004599 / NHGRI NIH HHS U01 HG008657 / NHGRI NIH HHS U01 HG006385 / NHGRI NIH HHS 084695 / Wellcome Trust UL1 TR001108 / NCATS NIH HHS UL1 RR025758 / NCRR NIH HHS U01 HG006382 / NHGRI NIH HHS HHSN268201100006C / NHLBI NIH HHS R03 NS083468 / NINDS NIH HHS UL1 TR000427 / NCATS NIH HHS HHSN268201100011C / NHLBI NIH HHS U01 HG006388 / NHGRI NIH HHS U01 HG004609 / NHGRI NIH HHS U01 HG004608 / NHGRI NIH HHS HHSN268201100010C / NHLBI NIH HHS UL1 RR025005 / NCRR NIH HHS HHSN268201100005C / NHLBI NIH HHS U01 HG006375 / NHGRI NIH HHS R01 HL059367 / NHLBI NIH HHS UL1 RR024148 / NCRR NIH HHS HHSN268201100008C / NHLBI NIH HHS U01 HG006380 / NHGRI NIH HHS U01 HG004438 / NHGRI NIH HHS U01 HG006378 / NHGRI NIH HHS R01 HL086694 / NHLBI NIH HHS 076113 / Wellcome Trust U01 HG004610 / NHGRI NIH HHS U01 HG006389 / NHGRI NIH HHS U01 HG004424 / NHGRI NIH HHS R01 HL087641 / NHLBI NIH HHS 085475 / Wellcome Trust U01 HG006379 / NHGRI NIH HHS
Identifiers: 9939536508331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article