Genetic and regulatory architecture of Alzheimer's disease in the APOE region.


Journal Article

Introduction:Apolipoprotein E (APOE) ε2 and ε4 alleles encoded by rs7412 and rs429358 polymorphisms, respectively, are landmark contra and pro "risk" factors for Alzheimer's disease (AD). Methods:We examined differences in linkage disequilibrium (LD) structures between (1) AD-affected and unaffected subjects and (2) older AD-unaffected and younger subjects in the 19q13.3 region harboring rs7412 and rs429358. Results:AD is associated with sex-nonspecific heterogeneous patterns of decreased and increased LD of rs7412 and rs429358, respectively, with other polymorphisms from five genes in this region in AD-affected subjects. The LD patterns in older AD-unaffected subjects resembled those in younger individuals. Polarization of the ε4- and ε2 allele-related heterogeneous LD clusters differentiated cell types and implicated specific tissues in AD pathogenesis. Discussion:Protection and predisposition to AD is characterized by an interplay of rs7412 and rs429358, with multiple polymorphisms in the 19q13.3 region in a tissue-specific manner, which is not driven by common evolutionary forces.

Full Text

Duke Authors

Cited Authors

  • Kulminski, AM; Shu, L; Loika, Y; He, L; Nazarian, A; Arbeev, K; Ukraintseva, S; Yashin, A; Culminskaya, I

Published Date

  • January 2020

Published In

Volume / Issue

  • 12 / 1

Start / End Page

  • e12008 -

PubMed ID

  • 32211503

Pubmed Central ID

  • 32211503

Electronic International Standard Serial Number (EISSN)

  • 2352-8729

International Standard Serial Number (ISSN)

  • 2352-8729

Digital Object Identifier (DOI)

  • 10.1002/dad2.12008


  • eng