title: Replication study of chr17q25 with cerebral white matter lesion volume.
abstract: OBJECTIVE
  Recently, the first genomewide association study on cerebral white matter lesion burden identified chr17q25 to be significantly associated with white matter lesions. We report on the first independent replication study of this genetic association.
  
  
  METHODS
  In a population-based cohort study, we investigated the association between the 6 genomewide significant single nucleotide polymorphisms at that locus and cerebral white matter lesion volume on MRI, measured quantitatively, adjusted for age, sex, and intracranial volume. Adjustments for ApoE4 carriership and cardiovascular risk factors were evaluated separately. Finally, we performed a meta-analysis of all published data for the single most significant single nucleotide polymorphism, rs3744028.
  
  
  RESULTS
  The risk alleles of all the 6 single nucleotide polymorphisms were significantly associated with white matter lesion volume with P=1.1*10(-3) for rs3744028, adjusted for age, sex, and intracranial volume. Additional adjustments only had minor influence on these associations. A meta-analysis with all published data for rs3744028 resulted in a probability value of 5.3*10(-17).
  
  
  CONCLUSIONS
  This study further establishes chr17q25 as a novel genetic locus for WML volume.
authors.affiliation: Department of Epidemiology, Erasmus MC University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Benjamin F J
authors.initials: BF
authors.lastname: Verhaaren
authors.forename: Renske
authors.initials: R
authors.lastname: de Boer
authors.forename: Meike W
authors.initials: MW
authors.lastname: Vernooij
authors.forename: Fernando
authors.initials: F
authors.lastname: Rivadeneira
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Gabriel P
authors.initials: GP
authors.lastname: Krestin
authors.forename: Aad
authors.initials: A
authors.lastname: van der Lugt
authors.forename: Wiro J
authors.initials: WJ
authors.lastname: Niessen
authors.forename: Monique M B
authors.initials: MM
authors.lastname: Breteler
authors.forename: M Arfan
authors.initials: MA
authors.lastname: Ikram
mesh_terms: D001921:Brain / Q000473:pathology; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D015331:Cohort Studies; D004261:DNA Replication / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D056784:Leukoencephalopathies / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011159:Population Surveillance / Q000379:methods