title: The association between genetic variants in SORL1 and Alzheimer disease in an urban, multiethnic, community-based cohort.
abstract: OBJECTIVE
  To investigate the association between Alzheimer disease (AD) and variant alleles in SORL1 using a series of single nucleotide polymorphisms (SNPs) in an urban, multiethnic, community-based population.
  
  
  METHODS
  We used a nested case-control analysis in a population-based, prospective study of aging and dementia in Medicare recipients, 65 years and older.
  
  
  METHODS
  Northern Manhattan, NY.
  
  
  METHODS
  There were 296 patients with probable AD and 428 healthy, elderly controls. The participants were African American (34%), Caribbean Hispanic (51%), or non-Hispanic white (15%).
  
  
  METHODS
  We genotyped all 29 SNPs in SORL1 that were examined in the earlier report. We assessed allelic association with AD using standard case-control methods, which included apolipoprotein E genotype as a covariate.
  
  
  RESULTS
  Several individual SNPs and SNP haplotypes were significantly associated with AD in this prospectively collected community-based cohort, confirming the previously reported positive association of SORL1 with AD. Single nucleotide polymorphism 12, near the 5' region, was associated with AD in African American and Hispanic individuals. Two SNPs in the 3' region were also associated with AD in African American (SNP 26) and non-Hispanic white (SNP 20) individuals. A single haplotype in the 3' region was associated with AD in Hispanic individuals. However, several different haplotypes were associated with AD in African American and white individuals, including the TTC haplotypes at SNPs 23 through 25 (P = .035), which was significantly associated with AD in the North European white individuals in our previous report.
  
  
  CONCLUSIONS
  This study confirms the association between genetic variants in SORL1 and AD. While the associations observed in these data sets overlap with those previously reported, the finding of novel SNP and haplotype associations suggests that there may be extensive allelic heterogeneity in SORL1. Broad regions of the SORL1 gene will therefore need to be scrutinized for functional pathogenic variants.
authors.affiliation: Taub Institute on Alzheimer's Disease and the Aging Brain, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Lee
authors.forename: Rong
authors.initials: R
authors.lastname: Cheng
authors.forename: Nicole
authors.initials: N
authors.lastname: Schupf
authors.forename: Jennifer
authors.initials: J
authors.lastname: Manly
authors.forename: Rafael
authors.initials: R
authors.lastname: Lantigua
authors.forename: Yaakov
authors.initials: Y
authors.lastname: Stern
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Rogaeva
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Wakutani
authors.forename: Lindsay
authors.initials: L
authors.lastname: Farrer
authors.forename: Peter
authors.initials: P
authors.lastname: St George-Hyslop
authors.forename: Richard
authors.initials: R
authors.lastname: Mayeux
mesh_terms: D001741:Black or African American / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D016009:Chi-Square Distribution; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D009518:New York; D020641:Polymorphism, Single Nucleotide; D014505:Urban Population / Q000706:statistics & numerical data*; D044465:White People / Q000235:genetics
chemical_list: D026502:LDL-Receptor Related Proteins; D026901:Membrane Transport Proteins; C102582:SORL1 protein, human