Genome-wide meta-analysis of cerebral white matter hyperintensities in patients with stroke

Matthew Traylor; Cathy R. Zhang; Poneh Adib-Samii; William J. Devan; Owen E. Parsons; Silvia Lanfranconi; Sarah Gregory; Lisa Cloonan; Guido J. Falcone; Farid Radmanesh; Kaitlin Fitzpatrick; Allison Kanakis; Thomas R. Barrick; Barry Moynihan; Cathryn M Lewis; Giorgio B. Boncoraglio; Robin Lemmens; Vincent Thijs; Cathie Sudlow; Joanna Wardlaw; Peter M. Rothwell; James F. Meschia; Bradford B. Worrall; Christopher Levi; Steve Bevan; Karen L. Furie; Martin Dichgans; Jonathan Rosand; Hugh S. Markus; Natalia Rost

doi:10.1212/WNL.0000000000002263

Genome-wide meta-analysis of cerebral white matter hyperintensities in patients with stroke

Matthew Traylor, Cathy R. Zhang, Poneh Adib-Samii, William J. Devan, Owen E. Parsons, Silvia Lanfranconi, Sarah Gregory, Lisa Cloonan, Guido J. Falcone, Farid Radmanesh, Kaitlin Fitzpatrick, Allison Kanakis, Thomas R. Barrick, Barry Moynihan, Cathryn M Lewis, Giorgio B. Boncoraglio, Robin Lemmens, Vincent Thijs, Cathie Sudlow, Joanna WardlawPeter M. Rothwell, James F. Meschia, Bradford B. Worrall, Christopher Levi, Steve Bevan, Karen L. Furie, Martin Dichgans, Jonathan Rosand, Hugh S. Markus, Natalia Rost

Western Sydney University

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

86 Citations (Scopus)

Abstract

Objective: For 3,670 stroke patients from the United Kingdom, United States, Australia, Belgium, and Italy, we performed a genome-wide meta-analysis of white matter hyperintensity volumes (WMHV) on data imputed to the 1000 Genomes reference dataset to provide insights into disease mechanisms. Methods: We first sought to identify genetic associations with white matter hyperintensities in a stroke population, and then examined whether genetic loci previously linked to WMHV in community populations are also associated in stroke patients. Having established that genetic associations are shared between the 2 populations, we performed a meta-analysis testing which associations with WMHV in stroke-free populations are associated overall when combined with stroke populations. Results: There were no associations at genome-wide significance with WMHV in stroke patients. All previously reported genome-wide significant associations with WMHV in community populations shared direction of effect in stroke patients. In a meta-analysis of the genome-wide significant and suggestive loci (p < 5 × 10-6) from community populations (15 single nucleotide polymorphisms in total) and from stroke patients, 6 independent loci were associated with WMHV in both populations. Four of these are novel associations at the genome-wide level (rs72934505 [NBEAL1], p 2.2 × 10-8; rs941898 [EVL], p 4.0 × 10-8; rs962888 [C1QL1], p 1.1 × 10-8; rs9515201 [COL4A2], p 6.9 × 10-9). Conclusions: Genetic associations with WMHV are shared in otherwise healthy individuals and patients with stroke, indicating common genetic susceptibility in cerebral small vessel disease. © 2015 American Academy of Neurology.

Original language	English
Pages (from-to)	146-153
Number of pages	8
Journal	Neurology
Volume	86
Issue number	2
DOIs	https://doi.org/10.1212/WNL.0000000000002263
Publication status	Published - 2016

Open Access - Access Right Statement

This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1212/WNL.0000000000002263

Cite this

Traylor, M., Zhang, C. R., Adib-Samii, P., Devan, W. J., Parsons, O. E., Lanfranconi, S., Gregory, S., Cloonan, L., Falcone, G. J., Radmanesh, F., Fitzpatrick, K., Kanakis, A., Barrick, T. R., Moynihan, B., Lewis, C. M., Boncoraglio, G. B., Lemmens, R., Thijs, V., Sudlow, C., ... Rost, N. (2016). Genome-wide meta-analysis of cerebral white matter hyperintensities in patients with stroke. Neurology, 86(2), 146-153. https://doi.org/10.1212/WNL.0000000000002263

@article{d75fe91ca300449ab91a2a0d5e898771,

title = "Genome-wide meta-analysis of cerebral white matter hyperintensities in patients with stroke",

abstract = "Objective: For 3,670 stroke patients from the United Kingdom, United States, Australia, Belgium, and Italy, we performed a genome-wide meta-analysis of white matter hyperintensity volumes (WMHV) on data imputed to the 1000 Genomes reference dataset to provide insights into disease mechanisms. Methods: We first sought to identify genetic associations with white matter hyperintensities in a stroke population, and then examined whether genetic loci previously linked to WMHV in community populations are also associated in stroke patients. Having established that genetic associations are shared between the 2 populations, we performed a meta-analysis testing which associations with WMHV in stroke-free populations are associated overall when combined with stroke populations. Results: There were no associations at genome-wide significance with WMHV in stroke patients. All previously reported genome-wide significant associations with WMHV in community populations shared direction of effect in stroke patients. In a meta-analysis of the genome-wide significant and suggestive loci (p < 5 × 10-6) from community populations (15 single nucleotide polymorphisms in total) and from stroke patients, 6 independent loci were associated with WMHV in both populations. Four of these are novel associations at the genome-wide level (rs72934505 [NBEAL1], p 2.2 × 10-8; rs941898 [EVL], p 4.0 × 10-8; rs962888 [C1QL1], p 1.1 × 10-8; rs9515201 [COL4A2], p 6.9 × 10-9). Conclusions: Genetic associations with WMHV are shared in otherwise healthy individuals and patients with stroke, indicating common genetic susceptibility in cerebral small vessel disease. {\textcopyright} 2015 American Academy of Neurology.",

author = "Matthew Traylor and Zhang, {Cathy R.} and Poneh Adib-Samii and Devan, {William J.} and Parsons, {Owen E.} and Silvia Lanfranconi and Sarah Gregory and Lisa Cloonan and Falcone, {Guido J.} and Farid Radmanesh and Kaitlin Fitzpatrick and Allison Kanakis and Barrick, {Thomas R.} and Barry Moynihan and Lewis, {Cathryn M} and Boncoraglio, {Giorgio B.} and Robin Lemmens and Vincent Thijs and Cathie Sudlow and Joanna Wardlaw and Rothwell, {Peter M.} and Meschia, {James F.} and Worrall, {Bradford B.} and Christopher Levi and Steve Bevan and Furie, {Karen L.} and Martin Dichgans and Jonathan Rosand and Markus, {Hugh S.} and Natalia Rost",

year = "2016",

doi = "10.1212/WNL.0000000000002263",

language = "English",

volume = "86",

pages = "146--153",

journal = "Neurology",

publisher = "Wolters Kluwer Health",

number = "2",

}

Traylor, M, Zhang, CR, Adib-Samii, P, Devan, WJ, Parsons, OE, Lanfranconi, S, Gregory, S, Cloonan, L, Falcone, GJ, Radmanesh, F, Fitzpatrick, K, Kanakis, A, Barrick, TR, Moynihan, B, Lewis, CM, Boncoraglio, GB, Lemmens, R, Thijs, V, Sudlow, C, Wardlaw, J, Rothwell, PM, Meschia, JF, Worrall, BB, Levi, C, Bevan, S, Furie, KL, Dichgans, M, Rosand, J, Markus, HS & Rost, N 2016, 'Genome-wide meta-analysis of cerebral white matter hyperintensities in patients with stroke', Neurology, vol. 86, no. 2, pp. 146-153. https://doi.org/10.1212/WNL.0000000000002263

TY - JOUR

T1 - Genome-wide meta-analysis of cerebral white matter hyperintensities in patients with stroke

AU - Traylor, Matthew

AU - Zhang, Cathy R.

AU - Adib-Samii, Poneh

AU - Devan, William J.

AU - Parsons, Owen E.

AU - Lanfranconi, Silvia

AU - Gregory, Sarah

AU - Cloonan, Lisa

AU - Falcone, Guido J.

AU - Radmanesh, Farid

AU - Fitzpatrick, Kaitlin

AU - Kanakis, Allison

AU - Barrick, Thomas R.

AU - Moynihan, Barry

AU - Lewis, Cathryn M

AU - Boncoraglio, Giorgio B.

AU - Lemmens, Robin

AU - Thijs, Vincent

AU - Sudlow, Cathie

AU - Wardlaw, Joanna

AU - Rothwell, Peter M.

AU - Meschia, James F.

AU - Worrall, Bradford B.

AU - Levi, Christopher

AU - Bevan, Steve

AU - Furie, Karen L.

AU - Dichgans, Martin

AU - Rosand, Jonathan

AU - Markus, Hugh S.

AU - Rost, Natalia

PY - 2016

Y1 - 2016

N2 - Objective: For 3,670 stroke patients from the United Kingdom, United States, Australia, Belgium, and Italy, we performed a genome-wide meta-analysis of white matter hyperintensity volumes (WMHV) on data imputed to the 1000 Genomes reference dataset to provide insights into disease mechanisms. Methods: We first sought to identify genetic associations with white matter hyperintensities in a stroke population, and then examined whether genetic loci previously linked to WMHV in community populations are also associated in stroke patients. Having established that genetic associations are shared between the 2 populations, we performed a meta-analysis testing which associations with WMHV in stroke-free populations are associated overall when combined with stroke populations. Results: There were no associations at genome-wide significance with WMHV in stroke patients. All previously reported genome-wide significant associations with WMHV in community populations shared direction of effect in stroke patients. In a meta-analysis of the genome-wide significant and suggestive loci (p < 5 × 10-6) from community populations (15 single nucleotide polymorphisms in total) and from stroke patients, 6 independent loci were associated with WMHV in both populations. Four of these are novel associations at the genome-wide level (rs72934505 [NBEAL1], p 2.2 × 10-8; rs941898 [EVL], p 4.0 × 10-8; rs962888 [C1QL1], p 1.1 × 10-8; rs9515201 [COL4A2], p 6.9 × 10-9). Conclusions: Genetic associations with WMHV are shared in otherwise healthy individuals and patients with stroke, indicating common genetic susceptibility in cerebral small vessel disease. © 2015 American Academy of Neurology.

AB - Objective: For 3,670 stroke patients from the United Kingdom, United States, Australia, Belgium, and Italy, we performed a genome-wide meta-analysis of white matter hyperintensity volumes (WMHV) on data imputed to the 1000 Genomes reference dataset to provide insights into disease mechanisms. Methods: We first sought to identify genetic associations with white matter hyperintensities in a stroke population, and then examined whether genetic loci previously linked to WMHV in community populations are also associated in stroke patients. Having established that genetic associations are shared between the 2 populations, we performed a meta-analysis testing which associations with WMHV in stroke-free populations are associated overall when combined with stroke populations. Results: There were no associations at genome-wide significance with WMHV in stroke patients. All previously reported genome-wide significant associations with WMHV in community populations shared direction of effect in stroke patients. In a meta-analysis of the genome-wide significant and suggestive loci (p < 5 × 10-6) from community populations (15 single nucleotide polymorphisms in total) and from stroke patients, 6 independent loci were associated with WMHV in both populations. Four of these are novel associations at the genome-wide level (rs72934505 [NBEAL1], p 2.2 × 10-8; rs941898 [EVL], p 4.0 × 10-8; rs962888 [C1QL1], p 1.1 × 10-8; rs9515201 [COL4A2], p 6.9 × 10-9). Conclusions: Genetic associations with WMHV are shared in otherwise healthy individuals and patients with stroke, indicating common genetic susceptibility in cerebral small vessel disease. © 2015 American Academy of Neurology.

UR - https://hdl.handle.net/1959.7/uws:64380

U2 - 10.1212/WNL.0000000000002263

DO - 10.1212/WNL.0000000000002263

M3 - Article

VL - 86

SP - 146

EP - 153

JO - Neurology

JF - Neurology

IS - 2

ER -

Genome-wide meta-analysis of cerebral white matter hyperintensities in patients with stroke

Abstract

Open Access - Access Right Statement

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this