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

Aneurysm Consortium, Vascular Research Consortium of New Zealand

Research output: Contribution to journalArticle

9 Citations (Scopus)

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 singlenucleotide 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=4.1910-5) and for TAA risk locus 15q21 near FBN1 to AAA (OR=1.07; P=1.1910-3). 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 (US)
Article numbere002603
JournalJournal of the American Heart Association
Volume5
Issue number7
DOIs
StatePublished - Jul 1 2016

Fingerprint

Abdominal Aortic Aneurysm
Thoracic Aortic Aneurysm
Intracranial Aneurysm
Aneurysm
Thorax
Odds Ratio
Genome-Wide Association Study
Linkage Disequilibrium
Single Nucleotide Polymorphism
Regression Analysis
Genome

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Aneurysm Consortium, Vascular Research Consortium of New Zealand. / Shared genetic risk factors of intracranial, abdominal, and thoracic aneurysms. In: Journal of the American Heart Association. 2016 ; Vol. 5, No. 7.
@article{a3f5a93baa364dee8d3b44ae611a2de0,
title = "Shared genetic risk factors of intracranial, abdominal, and thoracic aneurysms",
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 singlenucleotide 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=4.1910-5) and for TAA risk locus 15q21 near FBN1 to AAA (OR=1.07; P=1.1910-3). 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.",
author = "{Aneurysm Consortium, Vascular Research Consortium of New Zealand} and {van't Hof}, {Femke N.G.} and Ruigrok, {Ynte M.} and Lee, {Cue Hyunkyu} and Stephan Ripke and Graig Anderson and {de Andrade}, Mariza and Baas, {Annette F.} and Blankensteijn, {Jan D.} and B{\"o}ttinger, {Erwin P.} and Bown, {Matthew J.} and Joseph Broderick and Philippe Bijlenga and Carrell, {David S.} and Crawford, {Dana C.} and Crosslin, {David R.} and Christian Ebeling and Eriksson, {Johan G.} and Myriam Fornage and Tatiana Foroud and {von und zu Fraunberg}, Mikael and Friedrich, {Christoph M.} and Ga{\'a}l, {Em{\'i}lia I.} and Omri Gottesman and Guo, {Dong Chuan} and Harrison, {Seamus C.} and Juha Hernesniemi and Albert Hofman and Ituro Inoue and J{\"a}{\"a}skel{\"a}inen, {Juha E.} and Jones, {Gregory T.} and Kiemeney, {Lambertus A.L.M.} and Riku Kivisaari and Nerissa Ko and Seppo Koskinen and Michiaki Kubo and Kullo, {Iftikhar J.} and Helena Kuivaniemi and Kurki, {Mitja I.} and Aki Laakso and Dongbing Lai and Leal, {Suzanne M.} and Hanna Lehto and LeMaire, {Scott A.} and Low, {Siew Kee} and Jennifer Malinowski and McCarty, {Catherine A.} and Milewicz, {Dianna M.} and Mosley, {Thomas H.} and Yusuke Nakamura and Ritchie, {Marylyn Deriggi}",
year = "2016",
month = "7",
day = "1",
doi = "10.1161/JAHA.115.002603",
language = "English (US)",
volume = "5",
journal = "Journal of the American Heart Association",
issn = "2047-9980",
publisher = "Wiley-Blackwell",
number = "7",

}

Shared genetic risk factors of intracranial, abdominal, and thoracic aneurysms. / Aneurysm Consortium, Vascular Research Consortium of New Zealand.

In: Journal of the American Heart Association, Vol. 5, No. 7, e002603, 01.07.2016.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Shared genetic risk factors of intracranial, abdominal, and thoracic aneurysms

AU - Aneurysm Consortium, Vascular Research Consortium of New Zealand

AU - van't Hof, Femke N.G.

AU - Ruigrok, Ynte M.

AU - Lee, Cue Hyunkyu

AU - Ripke, Stephan

AU - Anderson, Graig

AU - de Andrade, Mariza

AU - Baas, Annette F.

AU - Blankensteijn, Jan D.

AU - Böttinger, Erwin P.

AU - Bown, Matthew J.

AU - Broderick, Joseph

AU - Bijlenga, Philippe

AU - Carrell, David S.

AU - Crawford, Dana C.

AU - Crosslin, David R.

AU - Ebeling, Christian

AU - Eriksson, Johan G.

AU - Fornage, Myriam

AU - Foroud, Tatiana

AU - von und zu Fraunberg, Mikael

AU - Friedrich, Christoph M.

AU - Gaál, Emília I.

AU - Gottesman, Omri

AU - Guo, Dong Chuan

AU - Harrison, Seamus C.

AU - Hernesniemi, Juha

AU - Hofman, Albert

AU - Inoue, Ituro

AU - Jääskeläinen, Juha E.

AU - Jones, Gregory T.

AU - Kiemeney, Lambertus A.L.M.

AU - Kivisaari, Riku

AU - Ko, Nerissa

AU - Koskinen, Seppo

AU - Kubo, Michiaki

AU - Kullo, Iftikhar J.

AU - Kuivaniemi, Helena

AU - Kurki, Mitja I.

AU - Laakso, Aki

AU - Lai, Dongbing

AU - Leal, Suzanne M.

AU - Lehto, Hanna

AU - LeMaire, Scott A.

AU - Low, Siew Kee

AU - Malinowski, Jennifer

AU - McCarty, Catherine A.

AU - Milewicz, Dianna M.

AU - Mosley, Thomas H.

AU - Nakamura, Yusuke

AU - Ritchie, Marylyn Deriggi

PY - 2016/7/1

Y1 - 2016/7/1

N2 - 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 singlenucleotide 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=4.1910-5) and for TAA risk locus 15q21 near FBN1 to AAA (OR=1.07; P=1.1910-3). 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.

AB - 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 singlenucleotide 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=4.1910-5) and for TAA risk locus 15q21 near FBN1 to AAA (OR=1.07; P=1.1910-3). 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.

UR - http://www.scopus.com/inward/record.url?scp=85018786631&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85018786631&partnerID=8YFLogxK

U2 - 10.1161/JAHA.115.002603

DO - 10.1161/JAHA.115.002603

M3 - Article

VL - 5

JO - Journal of the American Heart Association

JF - Journal of the American Heart Association

SN - 2047-9980

IS - 7

M1 - e002603

ER -