Gene Co-Expression Analysis of Multiple Brain Tissues Reveals Correlation of FAM222A Expression with Multiple Alzheimer's Disease-Related Genes

Jingjing Liang, Bonnie Lafleur, Sadiya Hussainy, George Perry, Daniela Galimberti

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Background: Alzheimer's disease (AD) is the most common form of dementia in the elderly marked by central nervous system (CNS) neuronal loss and amyloid plaques. FAM222A, encoding an amyloid plaque core protein, is an AD brain atrophy susceptibility gene that mediates amyloid-β aggregation. However, the expression interplay between FAM222A and other AD-related pathway genes is unclear. Objective: Our goal was to study FAM222A's whole-genome co-expression profile in multiple tissues and investigate its interplay with other AD-related genes. Methods: We analyzed gene expression correlations in Genotype-Tissue Expression (GTEx) tissues to identify FAM222A co-expressed genes and performed functional enrichment analysis on identified genes in CNS system. Results: Genome-wide gene expression profiling identified 673 genes significantly correlated with FAM222A (p < 2.5×10-6) in 48 human tissues, including 298 from 13 CNS tissues. Functional enrichment analysis revealed that FAM222A co-expressed CNS genes were enriched in multiple AD-related pathways. Gene co-expression network analysis for identified genes in each brain region predicted other disease associated genes with similar biological function. Furthermore, co-expression of 25 out of 31 AD-related pathways genes with FAM222A was replicated in brain samples from 107 aged subjects from the Aging, Dementia and TBI Study. Conclusion: This gene co-expression study identified multiple AD-related genes that are associated with FAM222A, indicating that FAM222A and AD-associated genes can be active simultaneously in similar biological processes, providing evidence that supports the association of FAM222A with AD.

Original languageEnglish (US)
Article number1
Pages (from-to)S249-S263
JournalJournal of Alzheimer's Disease
Volume99
Issue numbers2
DOIs
StatePublished - May 7 2024

Keywords

  • Alzheimer's disease
  • FAM222A
  • gene co-expression network analysis
  • neurodegeneration
  • transcriptomics

ASJC Scopus subject areas

  • General Neuroscience
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

Fingerprint

Dive into the research topics of 'Gene Co-Expression Analysis of Multiple Brain Tissues Reveals Correlation of FAM222A Expression with Multiple Alzheimer's Disease-Related Genes'. Together they form a unique fingerprint.

Cite this