title: Association of Chr17q25 with cerebral white matter hyperintensities and cognitive impairment: the J-SHIPP study.
abstract: OBJECTIVE
  A recent genome-wide association study has successfully identified several genetic variations in the Chr17q25 locus as susceptible genotypes for white matter hyperintensities. We report the first replication study in subjects of non-European origin. We also investigated possible associations with other asymptomatic cerebrovascular diseases and cognitive function.
  
  
  METHODS
  Study subjects were 1190 general Japanese persons (66.0 ± 8.9 years old). Asymptomatic cerebrovascular damage, including lacunar infarctions, microbleeds, periventricular hyperintensity and deep and subcortical white matter hyperintensity (DSWMH), was evaluated by brain magnetic resonance imaging.
  
  
  RESULTS
  A polymorphism rs3744028 was significantly associated with DSWMH grade (P = 0.015) but not periventricular hyperintensity, lacunar infarction, and microbleeds. Although age, hypertension, insulin resistance, B-type natriuretic peptide, and carotid atherosclerosis were also correlated with DSWMH, association of the genotype was independent of these environmental risk factors. In contrast, the risk allele had a protective effect against reduced cognitive function.
  
  
  CONCLUSIONS
  Susceptibility of the 17q25 locus may be conserved beyond ethnic differences. Genetic variants may have bipolar effects on brain histological and functional changes.
authors.affiliation: Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan. tabara@genome.med.kyotou.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Tabara
authors.forename: M
authors.initials: M
authors.lastname: Igase
authors.forename: Y
authors.initials: Y
authors.lastname: Okada
authors.forename: T
authors.initials: T
authors.lastname: Nagai
authors.forename: E
authors.initials: E
authors.lastname: Uetani
authors.forename: T
authors.initials: T
authors.lastname: Kido
authors.forename: N
authors.initials: N
authors.lastname: Ochi
authors.forename: R
authors.initials: R
authors.lastname: Takita
authors.forename: M
authors.initials: M
authors.lastname: Yamamoto
authors.forename: K
authors.initials: K
authors.lastname: Kohara
authors.forename: T
authors.initials: T
authors.lastname: Miki
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics / Q000523:psychology; D002561:Cerebrovascular Disorders / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D003072:Cognition Disorders / Q000235:genetics* / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D059906:Neuroimaging / Q000523:psychology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics