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.
authors.affiliation: Authors' affiliations are listed at the end of the article. mt628@medschl.cam.ac.uk.
authors.forename: Matthew
authors.initials: M
authors.lastname: Traylor
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authors.forename: Cathy R
authors.initials: CR
authors.lastname: Zhang
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authors.forename: Poneh
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authors.lastname: Adib-Samii
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authors.forename: William J
authors.initials: WJ
authors.lastname: Devan
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authors.forename: Owen E
authors.initials: OE
authors.lastname: Parsons
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authors.forename: Silvia
authors.initials: S
authors.lastname: Lanfranconi
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authors.forename: Sarah
authors.initials: S
authors.lastname: Gregory
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authors.forename: Lisa
authors.initials: L
authors.lastname: Cloonan
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authors.forename: Guido J
authors.initials: GJ
authors.lastname: Falcone
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authors.forename: Farid
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authors.lastname: Radmanesh
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authors.forename: Kaitlin
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authors.lastname: Fitzpatrick
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authors.forename: Allison
authors.initials: A
authors.lastname: Kanakis
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authors.forename: Thomas R
authors.initials: TR
authors.lastname: Barrick
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authors.forename: Barry
authors.initials: B
authors.lastname: Moynihan
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authors.forename: Cathryn M
authors.initials: CM
authors.lastname: Lewis
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authors.forename: Giorgio B
authors.initials: GB
authors.lastname: Boncoraglio
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authors.forename: Robin
authors.initials: R
authors.lastname: Lemmens
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authors.forename: Vincent
authors.initials: V
authors.lastname: Thijs
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authors.forename: Cathie
authors.initials: C
authors.lastname: Sudlow
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authors.forename: Joanna
authors.initials: J
authors.lastname: Wardlaw
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authors.forename: Peter M
authors.initials: PM
authors.lastname: Rothwell
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authors.forename: James F
authors.initials: JF
authors.lastname: Meschia
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authors.forename: Bradford B
authors.initials: BB
authors.lastname: Worrall
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authors.forename: Christopher
authors.initials: C
authors.lastname: Levi
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authors.forename: Steve
authors.initials: S
authors.lastname: Bevan
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authors.forename: Karen L
authors.initials: KL
authors.lastname: Furie
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authors.forename: Martin
authors.initials: M
authors.lastname: Dichgans
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authors.forename: Jonathan
authors.initials: J
authors.lastname: Rosand
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authors.forename: Hugh S
authors.initials: HS
authors.lastname: Markus
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authors.forename: Natalia
authors.initials: N
authors.lastname: Rost
mesh_terms: D059345:Cerebral Small Vessel Diseases / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing / Q000379:methods; D055106:Genome-Wide Association Study; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology* / Q000503:physiopathology; D066127:White Matter / Q000503:physiopathology*