title: Age-Related Macular Degeneration-Associated Genes in Alzheimer Disease.
abstract: OBJECTIVE
  Given the clinical and pathological similarities between age-related macular degeneration (AMD) and Alzheimer disease (AD), to assess whether AMD-associated single nucleotide polymorphisms (SNPs), including those from complement-related genes, are associated with AD.
  
  
  METHODS
  A case-control association study-type design.
  
  
  METHODS
  A UK tertiary care dementia clinic.
  
  
  METHODS
  322 cognitively normal participants and 258 cases with a clinical diagnosis of AD.
  
  
  METHODS
  Polymorphisms in the following genes were studied: CFH, ARMS2, C2/CFB, C3, CFI/PLA2G12a, SERPING1, TLR3, TLR4, CRP, APOE, and TOMM40. Haplotypes were analysed for CFH, TOMM40, and APOE. Univariate analysis was performed for each genetic change and case-comparator status, and then correction for multiple testing performed.
  
  
  RESULTS
  The presence of an ε4 APOE allele was significantly associated with AD. No association was evident between CFH SNPs or haplotypes, or other AMD-associated SNPs tested, and AD. The exceptions were TOMM40 SNPs, which were associated with AD even after correction for multiple comparisons. The associations disappeared, however, when entered into a regression model including APOE genotypes.
  
  
  CONCLUSIONS
  The results for most SNPs tested, as well as CFH haplotypes, are novel. The functional effects of abnormal complement activity in AD's pathogenesis may be contradictory, but methodological reasons may underlie the lack of association-for example, genetic changes other than SNPs being involved.
authors.affiliation: Centre for Medical Education, Queen's University of Belfast, UK. Electronic address: m.williams@qub.ac.uk.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Williams
authors.affiliation: Centre for Public Health, Queen's University of Belfast, UK.
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: McKay
authors.affiliation: Centre for Public Health, Queen's University of Belfast, UK.
authors.forename: Robyn
authors.initials: R
authors.lastname: Carson
authors.affiliation: Centre for Public Health, Queen's University of Belfast, UK.
authors.forename: David
authors.initials: D
authors.lastname: Craig
authors.affiliation: Centre for Experimental Medicine (GS), Queen's University of Belfast, UK.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Silvestri
authors.affiliation: Centre for Public Health, Queen's University of Belfast, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Passmore
mesh_terms: D000367:Age Factors; D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D006113:United Kingdom
keywords: Alzheimer; complement; genetics