Integrative functional genomic analysis of intron retention in human and mouse brain with Alzheimer's disease

Hong Dong Li, Cory C. Funk, Karen McFarland, Eric B. Dammer, Mariet Allen, Minerva M. Carrasquillo, Yona Levites, Paramita Chakrabarty, Jeremy D. Burgess, Xue Wang, Dennis Dickson, Nicholas T. Seyfried, Duc M. Duong, James J. Lah, Steven G. Younkin, Allan I. Levey, Gilbert S. Omenn, Nilüfer Ertekin-Taner, Todd E. Golde, Nathan D. Price

Research output: Contribution to journalArticlepeer-review


Intron retention (IR) has been implicated in the pathogenesis of complex diseases such as cancers; its association with Alzheimer's disease (AD) remains unexplored. We performed genome-wide analysis of IR through integrating genetic, transcriptomic, and proteomic data of AD subjects and mouse models from the Accelerating Medicines Partnership-Alzheimer's Disease project. We identified 4535 and 4086 IR events in 2173 human and 1736 mouse genes, respectively. Quantitation of IR enabled the identification of differentially expressed genes that conventional exon-level approaches did not reveal. There were significant correlations of intron expression within innate immune genes, like HMBOX1, with AD in humans. Peptides with a high probability of translation from intron-retained mRNAs were identified using mass spectrometry. Further, we established AD-specific intron expression Quantitative Trait Loci, and identified splicing-related genes that may regulate IR. Our analysis provides a novel resource for the search for new AD biomarkers and pathological mechanisms.

Original languageEnglish (US)
Pages (from-to)984-1004
Number of pages21
JournalAlzheimer's and Dementia
Issue number6
StatePublished - Jun 2021


  • Alzheimer's disease
  • alternative splicing
  • gene expression
  • integrative analysis
  • intron retention

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Clinical Neurology
  • Geriatrics and Gerontology
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health


Dive into the research topics of 'Integrative functional genomic analysis of intron retention in human and mouse brain with Alzheimer's disease'. Together they form a unique fingerprint.

Cite this