title: 17q25 Locus is associated with white matter hyperintensity volume in ischemic stroke, but not with lacunar stroke status.
abstract: OBJECTIVE
  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 single-nucleotide 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.
authors.affiliation: Stroke and Dementia Research Centre, St George’s University of London, London, UK.
authors.forename: Poneh
authors.initials: P
authors.lastname: Adib-Samii
authors.forename: Natalia
authors.initials: N
authors.lastname: Rost
authors.forename: Matthew
authors.initials: M
authors.lastname: Traylor
authors.forename: William
authors.initials: W
authors.lastname: Devan
authors.forename: Alessandro
authors.initials: A
authors.lastname: Biffi
authors.forename: Silvia
authors.initials: S
authors.lastname: Lanfranconi
authors.forename: Kaitlin
authors.initials: K
authors.lastname: Fitzpatrick
authors.forename: Steve
authors.initials: S
authors.lastname: Bevan
authors.forename: Allison
authors.initials: A
authors.lastname: Kanakis
authors.forename: Valerie
authors.initials: V
authors.lastname: Valant
authors.forename: Andreas
authors.initials: A
authors.lastname: Gschwendtner
authors.forename: Rainer
authors.initials: R
authors.lastname: Malik
authors.forename: Alexa
authors.initials: A
authors.lastname: Richie
authors.forename: Dale
authors.initials: D
authors.lastname: Gamble
authors.forename: Helen
authors.initials: H
authors.lastname: Segal
authors.forename: Eugenio A
authors.initials: EA
authors.lastname: Parati
authors.forename: Emilio
authors.initials: E
authors.lastname: Ciusani
authors.forename: Elizabeth G
authors.initials: EG
authors.lastname: Holliday
authors.forename: Jane
authors.initials: J
authors.lastname: Maguire
authors.forename: Joanna
authors.initials: J
authors.lastname: Wardlaw
authors.forename: Bradford
authors.initials: B
authors.lastname: Worrall
authors.forename: Joshua
authors.initials: J
authors.lastname: Bis
authors.forename: Kerri L
authors.initials: KL
authors.lastname: Wiggins
authors.forename: Will
authors.initials: W
authors.lastname: Longstreth
authors.forename: Steve J
authors.initials: SJ
authors.lastname: Kittner
authors.forename: Yu-Ching
authors.initials: YC
authors.lastname: Cheng
authors.forename: Thomas
authors.initials: T
authors.lastname: Mosley
authors.forename: Guido J
authors.initials: GJ
authors.lastname: Falcone
authors.forename: Karen L
authors.initials: KL
authors.lastname: Furie
authors.forename: Carlos
authors.initials: C
authors.lastname: Leiva-Salinas
authors.forename: Benison C
authors.initials: BC
authors.lastname: Lau
authors.forename: Muhammed
authors.initials: M
authors.lastname: Saleem Khan
authors.forename: Pankaj
authors.initials: P
authors.lastname: Sharma
authors.forename: Myriam
authors.initials: M
authors.lastname: Fornage
authors.forename: Braxton D
authors.initials: BD
authors.lastname: Mitchell
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Psaty
authors.forename: Cathie
authors.initials: C
authors.lastname: Sudlow
authors.forename: Christopher
authors.initials: C
authors.lastname: Levi
authors.forename: Giorgio B
authors.initials: GB
authors.lastname: Boncoraglio
authors.forename: Peter M
authors.initials: PM
authors.lastname: Rothwell
authors.forename: James
authors.initials: J
authors.lastname: Meschia
authors.forename: Martin
authors.initials: M
authors.lastname: Dichgans
authors.forename: Jonathan
authors.initials: J
authors.lastname: Rosand
authors.forename: Hugh S
authors.initials: HS
authors.lastname: Markus
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000473:pathology*; D016022:Case-Control Studies; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D020521:Stroke / Q000235:genetics* / Q000473:pathology*; D059409:Stroke, Lacunar / Q000235:genetics* / Q000473:pathology*
keywords: Genome-wide Association Study; genetics; leukoaraiosis; small-vessel disease; stroke