17q25 Locus is associated with white matter hyperintensity volume in ischemic stroke, but not with lacunar stroke status

Australian Stroke Genetics Collaborative; Poneh Adib-Samii; Natalia Rost; Matthew Traylor; William Devan; Alessandro Biffi; Silvia Lanfranconi; Kaitlin Fitzpatrick; Steve Bevan; Allison Kanakis; Valerie Valant; Andreas Gschwendtner; Rainer Malik; Alexa Richie; Dale Gamble; Helen Segal; Eugenio A Parati; Emilio Ciusani; Elizabeth G Holliday; Jane Maguire; Joanna Wardlaw; Bradford Worrall; Joshua Bis; Kerri L Wiggins; Will Longstreth; Steve J Kittner; Yu-Ching Cheng; Thomas Mosley; Guido J Falcone; Karen L Furie; Carlos Leiva-Salinas; Benison C Lau; Muhammed Saleem Khan; Pankaj Sharma; Myriam Fornage; Braxton D Mitchell; Bruce M Psaty; Cathie Sudlow; Christopher Levi; Giorgio B Boncoraglio; Peter M Rothwell; James Meschia; Martin Dichgans; Jonathan Rosand; Hugh S Markus

doi:10.1161/STROKEAHA.113.679936

17q25 Locus is associated with white matter hyperintensity volume in ischemic stroke, but not with lacunar stroke status

Australian Stroke Genetics Collaborative, Poneh Adib-Samii, Natalia Rost, Matthew Traylor, William Devan, Alessandro Biffi, Silvia Lanfranconi, Kaitlin Fitzpatrick, Steve Bevan, Allison Kanakis, Valerie Valant, Andreas Gschwendtner, Rainer Malik, Alexa Richie, Dale Gamble, Helen Segal, Eugenio A Parati, Emilio Ciusani, Elizabeth G Holliday, Jane MaguireJoanna Wardlaw, Bradford Worrall, Joshua Bis, Kerri L Wiggins, Will Longstreth, Steve J Kittner, Yu-Ching Cheng, Thomas Mosley, Guido J Falcone, Karen L Furie, Carlos Leiva-Salinas, Benison C Lau, Muhammed Saleem Khan, Pankaj Sharma, Myriam Fornage, Braxton D Mitchell, Bruce M Psaty, Cathie Sudlow, Christopher Levi, Giorgio B Boncoraglio, Peter M Rothwell, James Meschia, Martin Dichgans, Jonathan Rosand, Hugh S Markus

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

Abstract

BACKGROUND AND PURPOSE: Recently, a novel locus at 17q25 was associated with white matter hyperintensities (WMH) on MRI in stroke-free individuals. We aimed to replicate the association with WMH volume (WMHV) in patients with ischemic stroke. If the association acts by promoting a small vessel arteriopathy, it might be expected to also associate with lacunar stroke.

METHODS: We quantified WMH on MRI in the stroke-free hemisphere of 2588 ischemic stroke cases. Association between WMHV and 6 single-nucleotide polymorphisms at chromosome 17q25 was assessed by linear regression. These single-nucleotide polymorphisms were also investigated for association with lacunar stroke in 1854 cases and 51 939 stroke-free controls from METASTROKE. Meta-analyses with previous reports and a genetic risk score approach were applied to identify other novel WMHV risk variants and uncover shared genetic contributions to WMHV in community participants without stroke and ischemic stroke.

RESULTS: Single-nucleotide polymorphisms at 17q25 were associated with WMHV in ischemic stroke, the most significant being rs9894383 (P=0.0006). In contrast, there was no association between any single-nucleotide polymorphism and lacunar stroke. A genetic risk score analysis revealed further genetic components to WMHV shared between community participants without stroke and ischemic stroke.

CONCLUSIONS: This study provides support for an association between the 17q25 locus and WMH. In contrast, it is not associated with lacunar stroke, suggesting that the association does not act by promoting small-vessel arteriopathy or the same arteriopathy responsible for lacunar infarction.

Original language	English
Pages (from-to)	1609-15
Number of pages	7
Journal	Stroke; a journal of cerebral circulation
Volume	44
Issue number	6
DOIs	https://doi.org/10.1161/STROKEAHA.113.679936
Publication status	Published - Jun 2013

Keywords

Adult
Aged
Aged, 80 and over
Brain
Case-Control Studies
Chromosomes, Human, Pair 17
Female
Genome-Wide Association Study
Genotype
Humans
Linear Models
Magnetic Resonance Imaging
Male
Middle Aged
Nerve Fibers, Myelinated
Polymorphism, Single Nucleotide
Stroke
Stroke, Lacunar

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10.1161/STROKEAHA.113.679936

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Australian Stroke Genetics Collaborative, Adib-Samii, P., Rost, N., Traylor, M., Devan, W., Biffi, A., Lanfranconi, S., Fitzpatrick, K., Bevan, S., Kanakis, A., Valant, V., Gschwendtner, A., Malik, R., Richie, A., Gamble, D., Segal, H., Parati, E. A., Ciusani, E., Holliday, E. G., ... Markus, H. S. (2013). 17q25 Locus is associated with white matter hyperintensity volume in ischemic stroke, but not with lacunar stroke status. Stroke; a journal of cerebral circulation, 44(6), 1609-15. https://doi.org/10.1161/STROKEAHA.113.679936

@article{4d50c6034bef416abd36f4c4fb165ab2,

title = "17q25 Locus is associated with white matter hyperintensity volume in ischemic stroke, but not with lacunar stroke status",

abstract = "BACKGROUND AND PURPOSE: Recently, a novel locus at 17q25 was associated with white matter hyperintensities (WMH) on MRI in stroke-free individuals. We aimed to replicate the association with WMH volume (WMHV) in patients with ischemic stroke. If the association acts by promoting a small vessel arteriopathy, it might be expected to also associate with lacunar stroke.METHODS: We quantified WMH on MRI in the stroke-free hemisphere of 2588 ischemic stroke cases. Association between WMHV and 6 single-nucleotide polymorphisms at chromosome 17q25 was assessed by linear regression. These single-nucleotide polymorphisms were also investigated for association with lacunar stroke in 1854 cases and 51 939 stroke-free controls from METASTROKE. Meta-analyses with previous reports and a genetic risk score approach were applied to identify other novel WMHV risk variants and uncover shared genetic contributions to WMHV in community participants without stroke and ischemic stroke.RESULTS: Single-nucleotide polymorphisms at 17q25 were associated with WMHV in ischemic stroke, the most significant being rs9894383 (P=0.0006). In contrast, there was no association between any single-nucleotide polymorphism and lacunar stroke. A genetic risk score analysis revealed further genetic components to WMHV shared between community participants without stroke and ischemic stroke.CONCLUSIONS: This study provides support for an association between the 17q25 locus and WMH. In contrast, it is not associated with lacunar stroke, suggesting that the association does not act by promoting small-vessel arteriopathy or the same arteriopathy responsible for lacunar infarction.",

keywords = "Adult, Aged, Aged, 80 and over, Brain, Case-Control Studies, Chromosomes, Human, Pair 17, Female, Genome-Wide Association Study, Genotype, Humans, Linear Models, Magnetic Resonance Imaging, Male, Middle Aged, Nerve Fibers, Myelinated, Polymorphism, Single Nucleotide, Stroke, Stroke, Lacunar",

author = "{Australian Stroke Genetics Collaborative} and Poneh Adib-Samii and Natalia Rost and Matthew Traylor and William Devan and Alessandro Biffi and Silvia Lanfranconi and Kaitlin Fitzpatrick and Steve Bevan and Allison Kanakis and Valerie Valant and Andreas Gschwendtner and Rainer Malik and Alexa Richie and Dale Gamble and Helen Segal and Parati, {Eugenio A} and Emilio Ciusani and Holliday, {Elizabeth G} and Jane Maguire and Joanna Wardlaw and Bradford Worrall and Joshua Bis and Wiggins, {Kerri L} and Will Longstreth and Kittner, {Steve J} and Yu-Ching Cheng and Thomas Mosley and Falcone, {Guido J} and Furie, {Karen L} and Carlos Leiva-Salinas and Lau, {Benison C} and {Saleem Khan}, Muhammed and Pankaj Sharma and Myriam Fornage and Mitchell, {Braxton D} and Psaty, {Bruce M} and Cathie Sudlow and Christopher Levi and Boncoraglio, {Giorgio B} and Rothwell, {Peter M} and James Meschia and Martin Dichgans and Jonathan Rosand and Markus, {Hugh S}",

note = "Date of Acceptance: 04/03/2015",

year = "2013",

month = jun,

doi = "10.1161/STROKEAHA.113.679936",

language = "English",

volume = "44",

pages = "1609--15",

journal = "Stroke",

issn = "0039-2499",

publisher = "Lippincott Williams & Wilkins",

number = "6",

}

Australian Stroke Genetics Collaborative, Adib-Samii, P, Rost, N, Traylor, M, Devan, W, Biffi, A, Lanfranconi, S, Fitzpatrick, K, Bevan, S, Kanakis, A, Valant, V, Gschwendtner, A, Malik, R, Richie, A, Gamble, D, Segal, H, Parati, EA, Ciusani, E, Holliday, EG, Maguire, J, Wardlaw, J, Worrall, B, Bis, J, Wiggins, KL, Longstreth, W, Kittner, SJ, Cheng, Y-C, Mosley, T, Falcone, GJ, Furie, KL, Leiva-Salinas, C, Lau, BC, Saleem Khan, M, Sharma, P, Fornage, M, Mitchell, BD, Psaty, BM, Sudlow, C, Levi, C, Boncoraglio, GB, Rothwell, PM, Meschia, J, Dichgans, M, Rosand, J & Markus, HS 2013, '17q25 Locus is associated with white matter hyperintensity volume in ischemic stroke, but not with lacunar stroke status', Stroke; a journal of cerebral circulation, vol. 44, no. 6, pp. 1609-15. https://doi.org/10.1161/STROKEAHA.113.679936

TY - JOUR

T1 - 17q25 Locus is associated with white matter hyperintensity volume in ischemic stroke, but not with lacunar stroke status

AU - Australian Stroke Genetics Collaborative

AU - Adib-Samii, Poneh

AU - Rost, Natalia

AU - Traylor, Matthew

AU - Devan, William

AU - Biffi, Alessandro

AU - Lanfranconi, Silvia

AU - Fitzpatrick, Kaitlin

AU - Bevan, Steve

AU - Kanakis, Allison

AU - Valant, Valerie

AU - Gschwendtner, Andreas

AU - Malik, Rainer

AU - Richie, Alexa

AU - Gamble, Dale

AU - Segal, Helen

AU - Parati, Eugenio A

AU - Ciusani, Emilio

AU - Holliday, Elizabeth G

AU - Maguire, Jane

AU - Wardlaw, Joanna

AU - Worrall, Bradford

AU - Bis, Joshua

AU - Wiggins, Kerri L

AU - Longstreth, Will

AU - Kittner, Steve J

AU - Cheng, Yu-Ching

AU - Mosley, Thomas

AU - Falcone, Guido J

AU - Furie, Karen L

AU - Leiva-Salinas, Carlos

AU - Lau, Benison C

AU - Saleem Khan, Muhammed

AU - Sharma, Pankaj

AU - Fornage, Myriam

AU - Mitchell, Braxton D

AU - Psaty, Bruce M

AU - Sudlow, Cathie

AU - Levi, Christopher

AU - Boncoraglio, Giorgio B

AU - Rothwell, Peter M

AU - Meschia, James

AU - Dichgans, Martin

AU - Rosand, Jonathan

AU - Markus, Hugh S

N1 - Date of Acceptance: 04/03/2015

PY - 2013/6

Y1 - 2013/6

N2 - BACKGROUND AND PURPOSE: Recently, a novel locus at 17q25 was associated with white matter hyperintensities (WMH) on MRI in stroke-free individuals. We aimed to replicate the association with WMH volume (WMHV) in patients with ischemic stroke. If the association acts by promoting a small vessel arteriopathy, it might be expected to also associate with lacunar stroke.METHODS: We quantified WMH on MRI in the stroke-free hemisphere of 2588 ischemic stroke cases. Association between WMHV and 6 single-nucleotide polymorphisms at chromosome 17q25 was assessed by linear regression. These single-nucleotide polymorphisms were also investigated for association with lacunar stroke in 1854 cases and 51 939 stroke-free controls from METASTROKE. Meta-analyses with previous reports and a genetic risk score approach were applied to identify other novel WMHV risk variants and uncover shared genetic contributions to WMHV in community participants without stroke and ischemic stroke.RESULTS: Single-nucleotide polymorphisms at 17q25 were associated with WMHV in ischemic stroke, the most significant being rs9894383 (P=0.0006). In contrast, there was no association between any single-nucleotide polymorphism and lacunar stroke. A genetic risk score analysis revealed further genetic components to WMHV shared between community participants without stroke and ischemic stroke.CONCLUSIONS: This study provides support for an association between the 17q25 locus and WMH. In contrast, it is not associated with lacunar stroke, suggesting that the association does not act by promoting small-vessel arteriopathy or the same arteriopathy responsible for lacunar infarction.

AB - BACKGROUND AND PURPOSE: Recently, a novel locus at 17q25 was associated with white matter hyperintensities (WMH) on MRI in stroke-free individuals. We aimed to replicate the association with WMH volume (WMHV) in patients with ischemic stroke. If the association acts by promoting a small vessel arteriopathy, it might be expected to also associate with lacunar stroke.METHODS: We quantified WMH on MRI in the stroke-free hemisphere of 2588 ischemic stroke cases. Association between WMHV and 6 single-nucleotide polymorphisms at chromosome 17q25 was assessed by linear regression. These single-nucleotide polymorphisms were also investigated for association with lacunar stroke in 1854 cases and 51 939 stroke-free controls from METASTROKE. Meta-analyses with previous reports and a genetic risk score approach were applied to identify other novel WMHV risk variants and uncover shared genetic contributions to WMHV in community participants without stroke and ischemic stroke.RESULTS: Single-nucleotide polymorphisms at 17q25 were associated with WMHV in ischemic stroke, the most significant being rs9894383 (P=0.0006). In contrast, there was no association between any single-nucleotide polymorphism and lacunar stroke. A genetic risk score analysis revealed further genetic components to WMHV shared between community participants without stroke and ischemic stroke.CONCLUSIONS: This study provides support for an association between the 17q25 locus and WMH. In contrast, it is not associated with lacunar stroke, suggesting that the association does not act by promoting small-vessel arteriopathy or the same arteriopathy responsible for lacunar infarction.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Brain

KW - Case-Control Studies

KW - Chromosomes, Human, Pair 17

KW - Female

KW - Genome-Wide Association Study

KW - Genotype

KW - Humans

KW - Linear Models

KW - Magnetic Resonance Imaging

KW - Male

KW - Middle Aged

KW - Nerve Fibers, Myelinated

KW - Polymorphism, Single Nucleotide

KW - Stroke

KW - Stroke, Lacunar

U2 - 10.1161/STROKEAHA.113.679936

DO - 10.1161/STROKEAHA.113.679936

M3 - Article

C2 - 23674528

VL - 44

SP - 1609

EP - 1615

JO - Stroke

JF - Stroke

SN - 0039-2499

IS - 6

ER -

17q25 Locus is associated with white matter hyperintensity volume in ischemic stroke, but not with lacunar stroke status

Abstract

Keywords

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