title: Impact of genetic variation in SORCS1 on memory retention.
abstract: OBJECTIVE
  We previously reported that genetic variants in SORCS1 increase the risk of AD, that over-expression of SorCS1 reduces γ-secretase activity and Aβ levels, and that SorCS1 suppression increases γ-secretase processing of APP and Aβ levels. We now explored the effect of variation in SORCS1 on memory.
  
  
  METHODS
  We explored associations between SORCS1-SNPs and memory retention in the NIA-LOAD case control dataset (162 cases,670 controls) and a cohort of Caribbean Hispanics (549 cases,544 controls) using single marker and haplotype analyses.
  
  
  RESULTS
  Three SNPs in intron 1, were associated with memory retention in the NIA-LOAD dataset or the Caribbean Hispanic dataset (rs10884402(A allele:β = -0.15,p = 0.008), rs7078098(C allele:β = 0.18,p = 0.007) and rs950809(C allele:β = 0.17,p = 0.008)) and all three SNPs were significant in a meta-analysis of both datasets (0.002<p<0.03). The corresponding A-T-T haplotype for these SNPs was associated with lower scores in both datasets (p = 0.02,p = 0.0009), and the complementary G-C-C haplotype was associated with higher scores in NIA-LOAD (p = 0.02). These associations were restricted to cases.
  
  
  CONCLUSIONS
  Variation in intron 1 in SORCS1 is associated with memory changes in AD.
authors: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York, United States of America.
authors: Christiane
authors: C
authors: Reitz
authors: Joseph H
authors: JH
authors: Lee
authors: Robert S
authors: RS
authors: Rogers
authors: Richard
authors: R
authors: Mayeux
mesh_terms: D016022:Case-Control Studies; D006630:Hispanic or Latino; D006801:Humans; D008568:Memory; D020641:Polymorphism, Single Nucleotide / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000235:genetics*
chemical_list: D011956:Receptors, Cell Surface; C472780:SORCS1 protein, human