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

Poneh Adib-Samii, William Devan, Matthew Traylor, Silvia Lanfranconi, Cathy R. Zhang, Lisa Cloonan, Guido J. Falcone, Farid Radmanesh, Kaitlin Fitzpatrick, Allison Kanakis, Peter M. Rothwell, Cathie Sudlow, Giorgio B. Boncoraglio, James F Meschia, Chris Levi, Martin Dichgans, Steve Bevan, Jonathan Rosand, Natalia S. Rost, Hugh S. Markus

Research output: Contribution to journalArticle

19 Citations (Scopus)

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); 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.

Original languageEnglish (US)
Pages (from-to)348-353
Number of pages6
JournalStroke
Volume46
Issue number2
DOIs
StatePublished - Feb 6 2015

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Single Nucleotide Polymorphism
Stroke
Genome-Wide Association Study
White Matter
Cerebrum
Epidemiologic Studies
Multivariate Analysis
Genome
Pathology

Keywords

  • genetics
  • hypertension
  • leukoaraiosis
  • stroke

ASJC Scopus subject areas

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

Cite this

Adib-Samii, P., Devan, W., Traylor, M., Lanfranconi, S., Zhang, C. R., Cloonan, L., ... Markus, H. S. (2015). Genetic architecture of white matter hyperintensities differs in hypertensive and nonhypertensive ischemic stroke. Stroke, 46(2), 348-353. https://doi.org/10.1161/STROKEAHA.114.006849

Genetic architecture of white matter hyperintensities differs in hypertensive and nonhypertensive ischemic stroke. / Adib-Samii, Poneh; Devan, William; Traylor, Matthew; Lanfranconi, Silvia; Zhang, Cathy R.; Cloonan, Lisa; Falcone, Guido J.; Radmanesh, Farid; Fitzpatrick, Kaitlin; Kanakis, Allison; Rothwell, Peter M.; Sudlow, Cathie; Boncoraglio, Giorgio B.; Meschia, James F; Levi, Chris; Dichgans, Martin; Bevan, Steve; Rosand, Jonathan; Rost, Natalia S.; Markus, Hugh S.

In: Stroke, Vol. 46, No. 2, 06.02.2015, p. 348-353.

Research output: Contribution to journalArticle

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 2015, 'Genetic architecture of white matter hyperintensities differs in hypertensive and nonhypertensive ischemic stroke', Stroke, vol. 46, no. 2, pp. 348-353. https://doi.org/10.1161/STROKEAHA.114.006849
Adib-Samii, Poneh ; Devan, William ; Traylor, Matthew ; Lanfranconi, Silvia ; Zhang, Cathy R. ; Cloonan, Lisa ; Falcone, Guido J. ; Radmanesh, Farid ; Fitzpatrick, Kaitlin ; Kanakis, Allison ; Rothwell, Peter M. ; Sudlow, Cathie ; Boncoraglio, Giorgio B. ; Meschia, James F ; Levi, Chris ; Dichgans, Martin ; Bevan, Steve ; Rosand, Jonathan ; Rost, Natalia S. ; Markus, Hugh S. / Genetic architecture of white matter hyperintensities differs in hypertensive and nonhypertensive ischemic stroke. In: Stroke. 2015 ; Vol. 46, No. 2. pp. 348-353.
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AU - Traylor, Matthew

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AU - Cloonan, Lisa

AU - Falcone, Guido J.

AU - Radmanesh, Farid

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