Skip to main content
Open Access Publications from the University of California

UC San Diego

UC San Diego Previously Published Works bannerUC San Diego

Non-coding variability at the APOE locus contributes to the Alzheimer's risk.

  • Author(s): Zhou, Xiaopu;
  • Chen, Yu;
  • Mok, Kin Y;
  • Kwok, Timothy CY;
  • Mok, Vincent CT;
  • Guo, Qihao;
  • Ip, Fanny C;
  • Chen, Yuewen;
  • Mullapudi, Nandita;
  • Alzheimer’s Disease Neuroimaging Initiative;
  • Giusti-Rodríguez, Paola;
  • Sullivan, Patrick F;
  • Hardy, John;
  • Fu, Amy KY;
  • Li, Yun;
  • Ip, Nancy Y
  • et al.

Alzheimer's disease (AD) is a leading cause of mortality in the elderly. While the coding change of APOE-ε4 is a key risk factor for late-onset AD and has been believed to be the only risk factor in the APOE locus, it does not fully explain the risk effect conferred by the locus. Here, we report the identification of AD causal variants in PVRL2 and APOC1 regions in proximity to APOE and define common risk haplotypes independent of APOE-ε4 coding change. These risk haplotypes are associated with changes of AD-related endophenotypes including cognitive performance, and altered expression of APOE and its nearby genes in the human brain and blood. High-throughput genome-wide chromosome conformation capture analysis further supports the roles of these risk haplotypes in modulating chromatin states and gene expression in the brain. Our findings provide compelling evidence for additional risk factors in the APOE locus that contribute to AD pathogenesis.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content
For improved accessibility of PDF content, download the file to your device.
Current View