The role of frontotemporal dementia associated genes in patients with Alzheimer's disease

Neurobiol Aging. 2021 Nov;107:153-158. doi: 10.1016/j.neurobiolaging.2021.05.016. Epub 2021 May 30.

Abstract

Alzheimer's disease (AD) and frontotemporal dementia (FTD) overlap clinically and pathologically. However, the role of FTD-associated genes in patients with AD remained unclear. To explore the relationship between FTD-associated genes and AD risk, we investigated 14 FTD-associated genes via targeted next-generation sequencing panel or whole-genome sequencing in a total of 721 AD patients and 1391 controls. Common variant-based association analysis and gene-based association test of rare variants were performed by PLINK 1.9 and Sequence Kernel Association Test-Optimal (SKAT-O test) respectively. As a result, 2 common variants, UBQLN1 rs1044175 (p value = 2.76 × 10-4) and MAPT rs2258689 (p value = 5.71 × 10-4), differed significantly between AD patients and controls. Additionally, gene-based analysis aggregating rare variants demonstrated that HNRNPA1 reached statistical significance in the SKAT-O test (p value = 2.24 × 10-3). Protein-protein interaction analysis showed that UBQLN1, MAPT, and HNRNPA1 interacted with proteins encoded by well-recognized AD-associated genes. Our study indicated that UBQLN1, MAPT, and HNRNPA1 are implicated in the pathogenesis of AD in the mainland Chinese population.

Keywords: Alzheimer's disease; Frontotemporal dementia; Genetic risk.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Aged
  • Alzheimer Disease / genetics*
  • Asian People / genetics
  • Autophagy-Related Proteins / genetics*
  • China
  • Female
  • Frontotemporal Dementia / genetics*
  • Genetic Association Studies / methods*
  • Heterogeneous Nuclear Ribonucleoprotein A1 / genetics*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Middle Aged
  • Protein Interaction Domains and Motifs / genetics
  • Whole Genome Sequencing
  • tau Proteins / genetics*

Substances

  • Adaptor Proteins, Signal Transducing
  • Autophagy-Related Proteins
  • Heterogeneous Nuclear Ribonucleoprotein A1
  • MAPT protein, human
  • UBQLN1 protein, human
  • hnRNPA1 protein, human
  • tau Proteins