Genome-wide association study of intracranial aneurysm identifies a new association on chromosome 7

Tatiana Foroud; Dongbing Lai; Daniel Koller; Femke Van't Hof; Mitja I. Kurki; Craig S. Anderson; Robert D. Brown; Edward Sander Connolly; Johan G. Eriksson; Matthew Flaherty; Myriam Fornage; Mikael Von Und Zu Fraunberg; Emília I. Gaál; Aki Laakso; Juha Hernesniemi; John Huston; Juha E. Jääskeläinen; Lambertus A. Kiemeney; Riku Kivisaari; Dawn Kleindorfer; Nerissa Ko; Hanna Lehto; Jason Mackey; Irene Meissner; Charles J. Moomaw; Thomas H. Mosley; Marek Moskala; Mika Niemelä; Aarno Palotie; Joanna Pera; Gabriel Rinkel; Stephan Ripke; Guy Rouleau; Ynte Ruigrok; Laura Sauerbeck; Agnieszka Słowik; Sita H. Vermeulen; Daniel Woo; Bradford B. Worrall; Joseph Broderick

doi:10.1161/STROKEAHA.114.006096

Genome-wide association study of intracranial aneurysm identifies a new association on chromosome 7

Tatiana Foroud, Dongbing Lai, Daniel Koller, Femke Van't Hof, Mitja I. Kurki, Craig S. Anderson, Robert D. Brown, Edward Sander Connolly, Johan G. Eriksson, Matthew Flaherty, Myriam Fornage, Mikael Von Und Zu Fraunberg, Emília I. Gaál, Aki Laakso, Juha Hernesniemi, John Huston, Juha E. Jääskeläinen, Lambertus A. Kiemeney, Riku Kivisaari, Dawn KleindorferNerissa Ko, Hanna Lehto, Jason Mackey, Irene Meissner, Charles J. Moomaw, Thomas H. Mosley, Marek Moskala, Mika Niemelä, Aarno Palotie, Joanna Pera, Gabriel Rinkel, Stephan Ripke, Guy Rouleau, Ynte Ruigrok, Laura Sauerbeck, Agnieszka Słowik, Sita H. Vermeulen, Daniel Woo, Bradford B. Worrall, Joseph Broderick

Research output: Contribution to journal › Article › peer-review

33 Scopus citations

Abstract

Background and Purpose-Common variants have been identified using genome-wide association studies which contribute to intracranial aneurysms (IA) susceptibility. However, it is clear that the variants identified to date do not account for the estimated genetic contribution to disease risk. Methods-Initial analysis was performed in a discovery sample of 2617 IA cases and 2548 controls of white ancestry. Novel chromosomal regions meeting genome-wide significance were further tested for association in 2 independent replication samples: Dutch (717 cases; 3004 controls) and Finnish (799 cases; 2317 controls). A meta-analysis was performed to combine the results from the 3 studies for key chromosomal regions of interest. Results-Genome-wide evidence of association was detected in the discovery sample on chromosome 9 (CDKN2BAS; rs10733376: P<1.0×10^-11), in a gene previously associated with IA. A novel region on chromosome 7, near HDAC9, was associated with IA (rs10230207; P=4.14×10^-8). This association replicated in the Dutch sample (P=0.01) but failed to show association in the Finnish sample (P=0.25). Meta-analysis results of the 3 cohorts reached statistical significant (P=9.91×10^-10). Conclusions-We detected a novel region associated with IA susceptibility that was replicated in an independent Dutch sample. This region on chromosome 7 has been previously associated with ischemic stroke and the large vessel stroke occlusive subtype (including HDAC9), suggesting a possible genetic link between this stroke subtype and IA.

Original language	English (US)
Pages (from-to)	3194-3199
Number of pages	6
Journal	Stroke
Volume	45
Issue number	11
DOIs	https://doi.org/10.1161/STROKEAHA.114.006096
State	Published - 2014

Keywords

Chromosomes
Genome-wide association study
Human
Intracranial aneurysm
Pair 7

ASJC Scopus subject areas

Clinical Neurology
Cardiology and Cardiovascular Medicine
Advanced and Specialized Nursing

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10.1161/STROKEAHA.114.006096

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Foroud, T., Lai, D., Koller, D., Van't Hof, F., Kurki, M. I., Anderson, C. S., Brown, R. D., Connolly, E. S., Eriksson, J. G., Flaherty, M., Fornage, M., Von Und Zu Fraunberg, M., Gaál, E. I., Laakso, A., Hernesniemi, J., Huston, J., Jääskeläinen, J. E., Kiemeney, L. A., Kivisaari, R., ... Broderick, J. (2014). Genome-wide association study of intracranial aneurysm identifies a new association on chromosome 7. Stroke, 45(11), 3194-3199. https://doi.org/10.1161/STROKEAHA.114.006096

Foroud, T, Lai, D, Koller, D, Van't Hof, F, Kurki, MI, Anderson, CS, Brown, RD, Connolly, ES, Eriksson, JG, Flaherty, M, Fornage, M, Von Und Zu Fraunberg, M, Gaál, EI, Laakso, A, Hernesniemi, J, Huston, J, Jääskeläinen, JE, Kiemeney, LA, Kivisaari, R, Kleindorfer, D, Ko, N, Lehto, H, Mackey, J, Meissner, I, Moomaw, CJ, Mosley, TH, Moskala, M, Niemelä, M, Palotie, A, Pera, J, Rinkel, G, Ripke, S, Rouleau, G, Ruigrok, Y, Sauerbeck, L, Słowik, A, Vermeulen, SH, Woo, D, Worrall, BB & Broderick, J 2014, 'Genome-wide association study of intracranial aneurysm identifies a new association on chromosome 7', Stroke, vol. 45, no. 11, pp. 3194-3199. https://doi.org/10.1161/STROKEAHA.114.006096

@article{73f3fa282d17495a9a4b3200f5560ee8,

title = "Genome-wide association study of intracranial aneurysm identifies a new association on chromosome 7",

abstract = "Background and Purpose-Common variants have been identified using genome-wide association studies which contribute to intracranial aneurysms (IA) susceptibility. However, it is clear that the variants identified to date do not account for the estimated genetic contribution to disease risk. Methods-Initial analysis was performed in a discovery sample of 2617 IA cases and 2548 controls of white ancestry. Novel chromosomal regions meeting genome-wide significance were further tested for association in 2 independent replication samples: Dutch (717 cases; 3004 controls) and Finnish (799 cases; 2317 controls). A meta-analysis was performed to combine the results from the 3 studies for key chromosomal regions of interest. Results-Genome-wide evidence of association was detected in the discovery sample on chromosome 9 (CDKN2BAS; rs10733376: P<1.0×10-11), in a gene previously associated with IA. A novel region on chromosome 7, near HDAC9, was associated with IA (rs10230207; P=4.14×10-8). This association replicated in the Dutch sample (P=0.01) but failed to show association in the Finnish sample (P=0.25). Meta-analysis results of the 3 cohorts reached statistical significant (P=9.91×10-10). Conclusions-We detected a novel region associated with IA susceptibility that was replicated in an independent Dutch sample. This region on chromosome 7 has been previously associated with ischemic stroke and the large vessel stroke occlusive subtype (including HDAC9), suggesting a possible genetic link between this stroke subtype and IA.",

keywords = "Chromosomes, Genome-wide association study, Human, Intracranial aneurysm, Pair 7",

author = "Tatiana Foroud and Dongbing Lai and Daniel Koller and {Van't Hof}, Femke and Kurki, {Mitja I.} and Anderson, {Craig S.} and Brown, {Robert D.} and Connolly, {Edward Sander} and Eriksson, {Johan G.} and Matthew Flaherty and Myriam Fornage and {Von Und Zu Fraunberg}, Mikael and Ga{\'a}l, {Em{\'i}lia I.} and Aki Laakso and Juha Hernesniemi and John Huston and J{\"a}{\"a}skel{\"a}inen, {Juha E.} and Kiemeney, {Lambertus A.} and Riku Kivisaari and Dawn Kleindorfer and Nerissa Ko and Hanna Lehto and Jason Mackey and Irene Meissner and Moomaw, {Charles J.} and Mosley, {Thomas H.} and Marek Moskala and Mika Niemel{\"a} and Aarno Palotie and Joanna Pera and Gabriel Rinkel and Stephan Ripke and Guy Rouleau and Ynte Ruigrok and Laura Sauerbeck and Agnieszka S{\l}owik and Vermeulen, {Sita H.} and Daniel Woo and Worrall, {Bradford B.} and Joseph Broderick",

note = "Publisher Copyright: {\textcopyright} 2014 American Heart Association, Inc.",

year = "2014",

doi = "10.1161/STROKEAHA.114.006096",

language = "English (US)",

volume = "45",

pages = "3194--3199",

journal = "Stroke",

issn = "0039-2499",

publisher = "Lippincott Williams and Wilkins",

number = "11",

}

TY - JOUR

T1 - Genome-wide association study of intracranial aneurysm identifies a new association on chromosome 7

AU - Foroud, Tatiana

AU - Lai, Dongbing

AU - Koller, Daniel

AU - Van't Hof, Femke

AU - Kurki, Mitja I.

AU - Anderson, Craig S.

AU - Brown, Robert D.

AU - Connolly, Edward Sander

AU - Eriksson, Johan G.

AU - Flaherty, Matthew

AU - Fornage, Myriam

AU - Von Und Zu Fraunberg, Mikael

AU - Gaál, Emília I.

AU - Laakso, Aki

AU - Hernesniemi, Juha

AU - Huston, John

AU - Jääskeläinen, Juha E.

AU - Kiemeney, Lambertus A.

AU - Kivisaari, Riku

AU - Kleindorfer, Dawn

AU - Ko, Nerissa

AU - Lehto, Hanna

AU - Mackey, Jason

AU - Meissner, Irene

AU - Moomaw, Charles J.

AU - Mosley, Thomas H.

AU - Moskala, Marek

AU - Niemelä, Mika

AU - Palotie, Aarno

AU - Pera, Joanna

AU - Rinkel, Gabriel

AU - Ripke, Stephan

AU - Rouleau, Guy

AU - Ruigrok, Ynte

AU - Sauerbeck, Laura

AU - Słowik, Agnieszka

AU - Vermeulen, Sita H.

AU - Woo, Daniel

AU - Worrall, Bradford B.

AU - Broderick, Joseph

PY - 2014

Y1 - 2014

N2 - Background and Purpose-Common variants have been identified using genome-wide association studies which contribute to intracranial aneurysms (IA) susceptibility. However, it is clear that the variants identified to date do not account for the estimated genetic contribution to disease risk. Methods-Initial analysis was performed in a discovery sample of 2617 IA cases and 2548 controls of white ancestry. Novel chromosomal regions meeting genome-wide significance were further tested for association in 2 independent replication samples: Dutch (717 cases; 3004 controls) and Finnish (799 cases; 2317 controls). A meta-analysis was performed to combine the results from the 3 studies for key chromosomal regions of interest. Results-Genome-wide evidence of association was detected in the discovery sample on chromosome 9 (CDKN2BAS; rs10733376: P<1.0×10-11), in a gene previously associated with IA. A novel region on chromosome 7, near HDAC9, was associated with IA (rs10230207; P=4.14×10-8). This association replicated in the Dutch sample (P=0.01) but failed to show association in the Finnish sample (P=0.25). Meta-analysis results of the 3 cohorts reached statistical significant (P=9.91×10-10). Conclusions-We detected a novel region associated with IA susceptibility that was replicated in an independent Dutch sample. This region on chromosome 7 has been previously associated with ischemic stroke and the large vessel stroke occlusive subtype (including HDAC9), suggesting a possible genetic link between this stroke subtype and IA.

AB - Background and Purpose-Common variants have been identified using genome-wide association studies which contribute to intracranial aneurysms (IA) susceptibility. However, it is clear that the variants identified to date do not account for the estimated genetic contribution to disease risk. Methods-Initial analysis was performed in a discovery sample of 2617 IA cases and 2548 controls of white ancestry. Novel chromosomal regions meeting genome-wide significance were further tested for association in 2 independent replication samples: Dutch (717 cases; 3004 controls) and Finnish (799 cases; 2317 controls). A meta-analysis was performed to combine the results from the 3 studies for key chromosomal regions of interest. Results-Genome-wide evidence of association was detected in the discovery sample on chromosome 9 (CDKN2BAS; rs10733376: P<1.0×10-11), in a gene previously associated with IA. A novel region on chromosome 7, near HDAC9, was associated with IA (rs10230207; P=4.14×10-8). This association replicated in the Dutch sample (P=0.01) but failed to show association in the Finnish sample (P=0.25). Meta-analysis results of the 3 cohorts reached statistical significant (P=9.91×10-10). Conclusions-We detected a novel region associated with IA susceptibility that was replicated in an independent Dutch sample. This region on chromosome 7 has been previously associated with ischemic stroke and the large vessel stroke occlusive subtype (including HDAC9), suggesting a possible genetic link between this stroke subtype and IA.

KW - Chromosomes

KW - Genome-wide association study

KW - Human

KW - Intracranial aneurysm

KW - Pair 7

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U2 - 10.1161/STROKEAHA.114.006096

DO - 10.1161/STROKEAHA.114.006096

M3 - Article

C2 - 25256182

AN - SCOPUS:84922479990

SN - 0039-2499

VL - 45

SP - 3194

EP - 3199

JO - Stroke

JF - Stroke

IS - 11

ER -

Genome-wide association study of intracranial aneurysm identifies a new association on chromosome 7

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Keywords

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