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

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 WardlawBradford 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 F Meschia, Martin Dichgans, Jonathan Rosand, Hugh S. Markus

Research output: Contribution to journalArticle

31 Citations (Scopus)

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 singlenucleotide 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 languageEnglish (US)
Pages (from-to)1609-1615
Number of pages7
JournalStroke
Volume44
Issue number6
DOIs
StatePublished - Jun 2013
Externally publishedYes

Fingerprint

Lacunar Stroke
Stroke
Single Nucleotide Polymorphism
White Matter
Meta-Analysis
Linear Models
Chromosomes

Keywords

  • Genetics
  • Genome-wide Association Study
  • Leukoaraiosis
  • Small-vessel disease
  • Stroke

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Advanced and Specialized Nursing

Cite this

Adib-Samii, P., Rost, N., Traylor, M., Devan, W., Biffi, A., Lanfranconi, S., ... Markus, H. S. (2013). 17q25 locus is associated with white matter hyperintensity volume in ischemic stroke, but not with lacunar stroke status. Stroke, 44(6), 1609-1615. https://doi.org/10.1161/STROKEAHA.113.679936

17q25 locus is associated with white matter hyperintensity volume in ischemic stroke, but not with lacunar stroke status. / Adib-Samii, Poneh; Rost, Natalia; Traylor, Matthew; Devan, William; Biffi, Alessandro; Lanfranconi, Silvia; Fitzpatrick, Kaitlin; Bevan, Steve; Kanakis, Allison; Valant, Valerie; Gschwendtner, Andreas; Malik, Rainer; Richie, Alexa; Gamble, Dale; Segal, Helen; Parati, Eugenio A.; Ciusani, Emilio; Holliday, Elizabeth G.; Maguire, Jane; Wardlaw, Joanna; Worrall, Bradford; Bis, Joshua; Wiggins, Kerri L.; Longstreth, Will; Kittner, Steve J.; Cheng, Yu Ching; Mosley, Thomas; Falcone, Guido J.; Furie, Karen L.; Leiva-Salinas, Carlos; Lau, Benison C.; Khan, Muhammed Saleem; Sharma, Pankaj; Fornage, Myriam; Mitchell, Braxton D.; Psaty, Bruce M.; Sudlow, Cathie; Levi, Christopher; Boncoraglio, Giorgio B.; Rothwell, Peter M.; Meschia, James F; Dichgans, Martin; Rosand, Jonathan; Markus, Hugh S.

In: Stroke, Vol. 44, No. 6, 06.2013, p. 1609-1615.

Research output: Contribution to journalArticle

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, YC, Mosley, T, Falcone, GJ, Furie, KL, Leiva-Salinas, C, Lau, BC, Khan, MS, Sharma, P, Fornage, M, Mitchell, BD, Psaty, BM, Sudlow, C, Levi, C, Boncoraglio, GB, Rothwell, PM, Meschia, JF, 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, vol. 44, no. 6, pp. 1609-1615. https://doi.org/10.1161/STROKEAHA.113.679936
Adib-Samii, Poneh ; Rost, Natalia ; Traylor, Matthew ; Devan, William ; Biffi, Alessandro ; Lanfranconi, Silvia ; Fitzpatrick, Kaitlin ; Bevan, Steve ; Kanakis, Allison ; Valant, Valerie ; Gschwendtner, Andreas ; Malik, Rainer ; Richie, Alexa ; Gamble, Dale ; Segal, Helen ; Parati, Eugenio A. ; Ciusani, Emilio ; Holliday, Elizabeth G. ; Maguire, Jane ; Wardlaw, Joanna ; Worrall, Bradford ; Bis, Joshua ; Wiggins, Kerri L. ; Longstreth, Will ; Kittner, Steve J. ; Cheng, Yu Ching ; Mosley, Thomas ; Falcone, Guido J. ; Furie, Karen L. ; Leiva-Salinas, Carlos ; Lau, Benison C. ; Khan, Muhammed Saleem ; Sharma, Pankaj ; Fornage, Myriam ; Mitchell, Braxton D. ; Psaty, Bruce M. ; Sudlow, Cathie ; Levi, Christopher ; Boncoraglio, Giorgio B. ; Rothwell, Peter M. ; Meschia, James F ; Dichgans, Martin ; Rosand, Jonathan ; Markus, Hugh S. / 17q25 locus is associated with white matter hyperintensity volume in ischemic stroke, but not with lacunar stroke status. In: Stroke. 2013 ; Vol. 44, No. 6. pp. 1609-1615.
@article{e9b7c51c047a4692a68dae4a7dcb1f1a,
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 singlenucleotide 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 = "Genetics, Genome-wide Association Study, Leukoaraiosis, Small-vessel disease, Stroke",
author = "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 Cheng, {Yu Ching} and Thomas Mosley and Falcone, {Guido J.} and Furie, {Karen L.} and Carlos Leiva-Salinas and Lau, {Benison C.} and Khan, {Muhammed Saleem} 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 Meschia, {James F} and Martin Dichgans and Jonathan Rosand and Markus, {Hugh S.}",
year = "2013",
month = "6",
doi = "10.1161/STROKEAHA.113.679936",
language = "English (US)",
volume = "44",
pages = "1609--1615",
journal = "Stroke",
issn = "0039-2499",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

TY - JOUR

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

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 - Khan, Muhammed Saleem

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 F

AU - Dichgans, Martin

AU - Rosand, Jonathan

AU - Markus, Hugh S.

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 singlenucleotide 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 singlenucleotide 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 - Genetics

KW - Genome-wide Association Study

KW - Leukoaraiosis

KW - Small-vessel disease

KW - Stroke

UR - http://www.scopus.com/inward/record.url?scp=84880180775&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84880180775&partnerID=8YFLogxK

U2 - 10.1161/STROKEAHA.113.679936

DO - 10.1161/STROKEAHA.113.679936

M3 - Article

C2 - 23674528

AN - SCOPUS:84880180775

VL - 44

SP - 1609

EP - 1615

JO - Stroke

JF - Stroke

SN - 0039-2499

IS - 6

ER -