The effects of the TOMM40 poly-T alleles on Alzheimer's disease phenotypes.

Journal Article (Journal Article;Review)

The TOMM40 poly-T is a polymorphism in intron 6 of the TOMM40 gene, which is adjacent to and in linkage disequilibrium with APOE. Roses et al. identified the association between the length of TOMM40 poly-T with the risk and age of onset of late-onset Alzheimer's disease (LOAD). Following the original discovery, additional studies found associations between the TOMM40 poly-T and LOAD-related phenotypes independent of APOE genotypes, while others did not replicate these associations. Furthermore, the identity of the TOMM40 poly-T risk allele has been controversial between different LOAD-related phenotypes. Here, we propose a framework to address the conflicting findings with respect to the TOMM40 poly-T allele associations with LOAD phenotypes and their functional effects. The framework is used to interpret previous studies as means to gain insights regarding the nature of the risk allele, very long versus short. We suggest that the identity of the TOMM40 poly-T risk allele depends on the phenotype being evaluated, the ages of the study subjects at the time of assessment, and the context of the APOE genotypes. In concluding remarks, we outline future studies that will inform the mechanistic interpretation of the genetic data.

Full Text

Duke Authors

Cited Authors

  • Chiba-Falek, O; Gottschalk, WK; Lutz, MW

Published Date

  • May 2018

Published In

Volume / Issue

  • 14 / 5

Start / End Page

  • 692 - 698

PubMed ID

  • 29524426

Pubmed Central ID

  • PMC5938113

Electronic International Standard Serial Number (EISSN)

  • 1552-5279

Digital Object Identifier (DOI)

  • 10.1016/j.jalz.2018.01.015


  • eng

Conference Location

  • United States