SORA

Advancing, promoting and sharing knowledge of health through excellence in teaching, clinical practice and research into the prevention and treatment of illness

Genetic architecture of white matter hyperintensities differs in hypertensive and nonhypertensive ischemic stroke.

Adib-Samii, P; Devan, W; Traylor, M; Lanfranconi, S; Zhang, CR; Cloonan, L; Falcone, GJ; Radmanesh, F; Fitzpatrick, K; Kanakis, A; et al. Adib-Samii, P; Devan, W; Traylor, M; Lanfranconi, S; Zhang, CR; Cloonan, L; Falcone, GJ; Radmanesh, F; Fitzpatrick, K; Kanakis, A; Rothwell, PM; Sudlow, C; Boncoraglio, GB; Meschia, JF; Levi, C; Dichgans, M; Bevan, S; Rosand, J; Rost, NS; Markus, HS (2014) Genetic architecture of white matter hyperintensities differs in hypertensive and nonhypertensive ischemic stroke. Stroke, 46 (2). pp. 348-353. ISSN 1524-4628 https://doi.org/10.1161/STROKEAHA.114.006849
SGUL Authors: Adib-Samii, Poneh

[img]
Preview
PDF Published Version
Available under License Creative Commons Attribution Non-commercial.

Download (2MB) | Preview

Abstract

BACKGROUND AND PURPOSE: Epidemiological studies suggest that white matter hyperintensities (WMH) are extremely heritable, but the underlying genetic variants are largely unknown. Pathophysiological heterogeneity is known to reduce the power of genome-wide association studies (GWAS). Hypertensive and nonhypertensive individuals with WMH might have different underlying pathologies. We used GWAS data to calculate the variance in WMH volume (WMHV) explained by common single nucleotide polymorphisms (SNPs) as a measure of heritability (SNP heritability [HSNP]) and tested the hypothesis that WMH heritability differs between hypertensive and nonhypertensive individuals. METHODS: WMHV was measured on MRI in the stroke-free cerebral hemisphere of 2336 ischemic stroke cases with GWAS data. After adjustment for age and intracranial volume, we determined which cardiovascular risk factors were independent predictors of WMHV. Using the genome-wide complex trait analysis tool to estimate HSNP for WMHV overall and within subgroups stratified by risk factors found to be significant in multivariate analyses. RESULTS: A significant proportion of the variance of WMHV was attributable to common SNPs after adjustment for significant risk factors (HSNP=0.23; P=0.0026). HSNP estimates were higher among hypertensive individuals (HSNP=0.45; P=7.99×10(-5)); this increase was greater than expected by chance (P=0.012). In contrast, estimates were lower, and nonsignificant, in nonhypertensive individuals (HSNP=0.13; P=0.13). CONCLUSIONS: A quarter of variance is attributable to common SNPs, but this estimate was greater in hypertensive individuals. These findings suggest that the genetic architecture of WMH in ischemic stroke differs between hypertensives and nonhypertensives. Future WMHV GWAS studies may gain power by accounting for this interaction.

Item Type: Article
Additional Information: © 2014 The Authors. Stroke is published on behalf of the American Heart Association, Inc., by Wolters Kluwer. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited and is not used for commercial purposes.
Keywords: genetics, hypertension, leukoaraiosis, stroke, Adult, Aged, Aged, 80 and over, Case-Control Studies, Cohort Studies, Female, Genome-Wide Association Study, Humans, Hypertension, Leukoencephalopathies, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors, Stroke, White Matter, Humans, Hypertension, Risk Factors, Case-Control Studies, Cohort Studies, Polymorphism, Single Nucleotide, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Stroke, Genome-Wide Association Study, Leukoencephalopathies, White Matter, genetics, hypertension, leukoaraiosis, stroke, Neurology & Neurosurgery, 1103 Clinical Sciences, 1102 Cardiovascular Medicine And Haematology, 1109 Neurosciences
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Neuroscience (INCCNS)
Journal or Publication Title: Stroke
ISSN: 1524-4628
Language: eng
Dates:
DateEvent
30 December 2014Published
Publisher License: Creative Commons: Attribution-Noncommercial 3.0
Projects:
Project IDFunderFunder ID
084724Wellcome Trusthttp://dx.doi.org/10.13039/100004440
095626Wellcome Trusthttp://dx.doi.org/10.13039/100004440
G0900295Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
K23 NS064052National Institute of Neurological Disorders and Strokehttp://dx.doi.org/10.13039/100000065
R01 NS039987National Institute of Neurological Disorders and Strokehttp://dx.doi.org/10.13039/100000065
R01 NS042733National Institute of Neurological Disorders and Strokehttp://dx.doi.org/10.13039/100000065
R01 NS082285National Institute of Neurological Disorders and Strokehttp://dx.doi.org/10.13039/100000065
U01 NS069208National Institute of Neurological Disorders and Strokehttp://dx.doi.org/10.13039/100000065
PubMed ID: 25550368
Web of Science ID: WOS:000348437800023
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/107749
Publisher's version: https://doi.org/10.1161/STROKEAHA.114.006849

Actions (login required)

Edit Item Edit Item