Investigation of 15 of the top candidate genes for late-onset Alzheimer's disease

Olivia Belbin, Minerva M Carrasquillo, Michael Crump, Oliver J Culley, Talisha A Hunter, Li Ma, Gina Bisceglio, Fanggeng Zou, Mariet Allen, Dennis W Dickson, Neill R Graff-Radford, Ronald C Petersen, Kevin Morgan, Steven G Younkin

Research output: Contribution to journalArticlepeer-review

Abstract

The 12 genome-wide association studies (GWAS) published to-date for late-onset Alzheimer's disease (LOAD) have identified over 40 candidate LOAD risk modifiers, in addition to apolipoprotein (APOE) ε4. A few of these novel LOAD candidate genes, namely BIN1, CLU, CR1, EXOC3L2 and PICALM, have shown consistent replication, and are thus credible LOAD susceptibility genes. To evaluate other promising LOAD candidate genes, we have added data from our large, case-control series (n=5,043) to meta-analyses of all published follow-up case-control association studies for six LOAD candidate genes that have shown significant association across multiple studies (TNK1, GAB2, LOC651924, GWA_14q32.13, PGBD1 and GALP) and for an additional nine previously suggested candidate genes. Meta-analyses remained significant at three loci after addition of our data: GAB2 (OR=0.78, p=0.007), LOC651924 (OR=0.91, p=0.01) and TNK1 (OR=0.92, p=0.02). Breslow-Day tests revealed significant heterogeneity between studies for GAB2 (p
Original languageEnglish
Pages (from-to)273-82
Number of pages10
JournalHuman Genetics
Volume129
Issue number3
DOIs
Publication statusPublished - Mar 2011

Keywords

  • Adaptor Proteins, Signal Transducing
  • Age of Onset
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Male
  • Middle Aged

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