title: Olfactory copy number association with age at onset of Alzheimer disease.
abstract: OBJECTIVE
  Copy number variants (CNVs) have been recognized as a source of genetic variation that contributes to disease phenotypes. Alzheimer disease (AD) has high heritability for occurrence and age at onset (AAO). We performed a cases-only genome-wide CNV association study for age at onset of AD.
  
  
  METHODS
  The discovery case series (n = 40 subjects with AD) was evaluated using array comparative genome hybridization (aCGH). A replication case series (n = 507 subjects with AD) was evaluated using Affymetrix array (n = 243) and multiplex ligation-dependent probe amplification (n = 264). Hazard models related onset age to CNV.
  
  
  RESULTS
  The discovery sample identified a chromosomal segment on 14q11.2 (19.3-19.5 Mb, NCBI build 36, UCSC hg18 March 2006) as a region of interest (genome-wide adjusted p = 0.032) for association with AAO of AD. This region encompasses a cluster of olfactory receptors. The replication sample confirmed the association (p = 0.035). The association was found for each APOE4 gene dosage (0, 1, and 2).
  
  
  CONCLUSIONS
  High copy number in the olfactory receptor region on 14q11.2 is associated with younger age at onset of AD.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Shaw
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: J
authors.initials: J
authors.lastname: Wiszniewska
authors.forename: S
authors.initials: S
authors.lastname: Chasse
authors.forename: S N Y
authors.initials: SN
authors.lastname: Zaidi
authors.forename: W
authors.initials: W
authors.lastname: Jin
authors.forename: B
authors.initials: B
authors.lastname: Dawson
authors.forename: K
authors.initials: K
authors.lastname: Wilhelmsen
authors.forename: J R
authors.initials: JR
authors.lastname: Lupski
authors.forename: J W
authors.initials: JW
authors.lastname: Belmont
authors.forename: R S
authors.initials: RS
authors.lastname: Doody
authors.forename: K
authors.initials: K
authors.lastname: Szigeti
mesh_terms: D017668:Age of Onset; D000544:Alzheimer Disease / Q000453:epidemiology* / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D015331:Cohort Studies; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D018628:Gene Dosage; D006801:Humans; D016016:Proportional Hazards Models; D018035:Receptors, Odorant / Q000235:genetics
chemical_list: D053327:Apolipoprotein E4; D018035:Receptors, Odorant