title: Meta-analysis of the association between variants in SORL1 and Alzheimer disease.
abstract: OBJECTIVE
  To reexamine the association between the neuronal sortilin-related receptor gene (SORL1) and Alzheimer disease (AD).
  
  
  METHODS
  Comprehensive and unbiased meta-analysis of all published and unpublished data from case-control studies for the SORL1 single-nucleotide polymorphisms (SNPs) that had been repeatedly assessed across studies.
  
  
  METHODS
  Academic research institutions in the United States, the Netherlands, Canada, Belgium, the United Kingdom, Singapore, Japan, Sweden, Germany, France, and Italy.
  
  
  METHODS
  All published white and Asian case-control data sets, which included a total of 12,464 cases and 17,929 controls.
  
  
  METHODS
  Alzheimer disease according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) and the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (now known as the Alzheimer's Association).
  
  
  RESULTS
  In the white data sets, several markers were associated with AD after correction for multiple testing, including previously reported SNPs 8, 9, and 10 (P < .001). In addition, the C-G-C haplotype at SNPs 8 through 10 was associated with AD risk (P < .001). In the combined Asian data sets, SNPs 19 and 23 through 25 were associated with AD risk (P < .001). The disease-associated alleles at SNPs 8, 9, and 10 (120,873,131-120,886,175 base pairs [bp]; C-G-C alleles), at SNP 19 (120,953,300 bp; G allele), and at SNPs 24 through 25 (120,988,611 bp; T and C alleles) were the same previously reported alleles. The SNPs 4 through 5, 8 through 10, 12, and 19 through 25 belong to distinct linkage disequilibrium blocks. The same alleles at SNPs 8 through 10 (C-G-C), 19 (G), and 24 and 25 (T and C) have also been associated with AD endophenotypes, including white matter hyperintensities and hippocampal atrophy on magnetic resonance imaging, cerebrospinal fluid measures of amyloid β-peptide 42, and full-length SORL1 expression in the human brain.
  
  
  CONCLUSIONS
  This comprehensive meta-analysis provides confirmatory evidence that multiple SORL1 variants in distinct linkage disequilibrium blocks are associated with AD.
authors.affiliation: The Taub Institute for Research on Alzheimer's Disease and the Aging Brain and the Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
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authors.forename: Ekaterina
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authors.forename: Joseph H
authors.initials: JH
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authors.forename: Shinya
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authors.forename: Fanggeng
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authors.lastname: Zou
authors.forename: Karolien
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authors.forename: Kristel
authors.initials: K
authors.lastname: Sleegers
authors.forename: Eng King
authors.initials: EK
authors.lastname: Tan
authors.forename: Ryo
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authors.lastname: Kimura
authors.forename: Nobuto
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authors.lastname: Shibata
authors.forename: Heii
authors.initials: H
authors.lastname: Arai
authors.forename: M Ilyas
authors.initials: MI
authors.lastname: Kamboh
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Prince
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Maier
authors.forename: Matthias
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authors.lastname: Riemenschneider
authors.forename: Michael
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authors.lastname: Owen
authors.forename: Denise
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authors.lastname: Harold
authors.forename: Paul
authors.initials: P
authors.lastname: Hollingworth
authors.forename: Elena
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authors.lastname: Cellini
authors.forename: Sandro
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authors.lastname: Sorbi
authors.forename: Benedetta
authors.initials: B
authors.lastname: Nacmias
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Takeda
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Pericak-Vance
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Haines
authors.forename: Steven
authors.initials: S
authors.lastname: Younkin
authors.forename: Julie
authors.initials: J
authors.lastname: Williams
authors.forename: Christine
authors.initials: C
authors.lastname: van Broeckhoven
authors.forename: Lindsay A
authors.initials: LA
authors.lastname: Farrer
authors.forename: Peter H
authors.initials: PH
authors.lastname: St George-Hyslop
authors.forename: Richard
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authors.lastname: Mayeux
mesh_terms: D000483:Alleles; D000544:Alzheimer Disease / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: D026502:LDL-Receptor Related Proteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C102582:SORL1 protein, human