Genetic association study on in and around the APOE in late-onset Alzheimer disease in Japanese

Norihiro Takei, Akinori Miyashita, Tamao Tsukie, Hiroyuki Arai, Takashi Asada, Masaki Imagawa, Mikio Shoji, Susumu Higuchi, Katsuya Urakami, Hideo Kimura, Akiyoshi Kakita, Hitoshi Takahashi, Shoji Tsuji, Ichiro Kanazawa, Yasuo Ihara, Shoji Odani, Ryozo Kuwano

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95 Citations (Scopus)

Abstract

The e{open}4 allele of APOE is a well-characterized genetic risk factor for late-onset Alzheimer disease (LOAD). Nevertheless, using high-density single nucleotide polymorphisms (SNPs), there have only been a few studies involving genetic association and linkage disequilibrium (LD) analyses of in and around the APOE. Here, we report fine mapping of a genomic region (about 200 kb) including the APOE in Japanese using 260 SNPs (mean intermaker distance, 0.77 kb). A case-control study demonstrated that 36 of these SNPs exhibited significance after adjustment for multiple testing. These SNPs are located in a genomic region including four genes, PVRL2, TOMM40, APOE and APOC1. Recombination rate estimation revealed that the associated region is firmly sandwiched between two recombination hotspots. Strong LD between these SNPs was observed (mean |D′| = 0.914). These data suggest that the three genes other than APOE, i.e. PVRL2, TOMM40 and APOC1, could also yield a predisposition to LOAD.

Original languageEnglish
Pages (from-to)441-448
Number of pages8
JournalGenomics
Volume93
Issue number5
DOIs
Publication statusPublished - 2009 May

Keywords

  • APOC1
  • APOE
  • Alzheimer disease
  • Association
  • Case-control study
  • Linkage disequilibrium
  • PVRL2
  • SNP
  • TOMM40

ASJC Scopus subject areas

  • Genetics

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    Takei, N., Miyashita, A., Tsukie, T., Arai, H., Asada, T., Imagawa, M., Shoji, M., Higuchi, S., Urakami, K., Kimura, H., Kakita, A., Takahashi, H., Tsuji, S., Kanazawa, I., Ihara, Y., Odani, S., & Kuwano, R. (2009). Genetic association study on in and around the APOE in late-onset Alzheimer disease in Japanese. Genomics, 93(5), 441-448. https://doi.org/10.1016/j.ygeno.2009.01.003