• Medientyp: E-Artikel
  • Titel: Non-coding variability at the APOE locus contributes to the Alzheimer’s risk
  • Beteiligte: Zhou, Xiaopu; Chen, Yu; Mok, Kin Y.; Kwok, Timothy C. Y.; Mok, Vincent C. T.; Guo, Qihao; Ip, Fanny C.; Chen, Yuewen; Mullapudi, Nandita; Weiner, Michael W.; Aisen, Paul; Petersen, Ronald; Jack, Clifford R.; Jagust, William; Trojanowski, John Q.; Toga, Arthur W.; Beckett, Laurel; Green, Robert C.; Saykin, Andrew J.; Morris, John; Shaw, Leslie M.; Khachaturian, Zaven; Sorensen, Greg; Kuller, Lew; [...]
  • Erschienen: Springer Science and Business Media LLC, 2019
  • Erschienen in: Nature Communications, 10 (2019) 1
  • Sprache: Englisch
  • DOI: 10.1038/s41467-019-10945-z
  • ISSN: 2041-1723
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  • Anmerkungen:
  • Beschreibung: AbstractAlzheimer’s disease (AD) is a leading cause of mortality in the elderly. While the coding change ofAPOE-ε4 is a key risk factor for late-onset AD and has been believed to be the only risk factor in theAPOElocus, it does not fully explain the risk effect conferred by the locus. Here, we report the identification of AD causal variants inPVRL2andAPOC1regions in proximity toAPOEand define common risk haplotypes independent ofAPOE-ε4 coding change. These risk haplotypes are associated with changes of AD-related endophenotypes including cognitive performance, and altered expression ofAPOEand 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 theAPOElocus that contribute to AD pathogenesis.
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