Joint genetic analysis of hippocampal size in mouse and human identifies a novel gene linked to neurodegenerative disease

David G. Ashbrook, Robert Williams, Lu Lu, Jason L. Stein, Derrek P. Hibar, Thomas E. Nichols, Sarah E. Medland, Paul M. Thompson, Reinmar Hager

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background: Variation in hippocampal volume has been linked to significant differences in memory, behavior, and cognition among individuals. To identify genetic variants underlying such differences and associated disease phenotypes, multinational consortia such as ENIGMA have used large magnetic resonance imaging (MRI) data sets in human GWAS studies. In addition, mapping studies in mouse model systems have identified genetic variants for brain structure variation with great power. A key challenge is to understand how genetically based differences in brain structure lead to the propensity to develop specific neurological disorders.Results: We combine the largest human GWAS of brain structure with the largest mammalian model system, the BXD recombinant inbred mouse population, to identify novel genetic targets influencing brain structure variation that are linked to increased risk for neurological disorders. We first use a novel cross-species, comparative analysis using mouse and human genetic data to identify a candidate gene, MGST3, associated with adult hippocampus size in both systems. We then establish the coregulation and function of this gene in a comprehensive systems-analysis.Conclusions: We find that MGST3 is associated with hippocampus size and is linked to a group of neurodegenerative disorders, such as Alzheimer's.

Original languageEnglish (US)
Article number850
JournalBMC Genomics
Volume15
Issue number1
DOIs
StatePublished - Oct 3 2014

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Neurodegenerative Diseases
Genome-Wide Association Study
Brain
Nervous System Diseases
Genes
Hippocampus
Medical Genetics
Systems Analysis
Cognition
Magnetic Resonance Imaging
Phenotype
Population

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Genetics

Cite this

Joint genetic analysis of hippocampal size in mouse and human identifies a novel gene linked to neurodegenerative disease. / Ashbrook, David G.; Williams, Robert; Lu, Lu; Stein, Jason L.; Hibar, Derrek P.; Nichols, Thomas E.; Medland, Sarah E.; Thompson, Paul M.; Hager, Reinmar.

In: BMC Genomics, Vol. 15, No. 1, 850, 03.10.2014.

Research output: Contribution to journalArticle

Ashbrook, David G. ; Williams, Robert ; Lu, Lu ; Stein, Jason L. ; Hibar, Derrek P. ; Nichols, Thomas E. ; Medland, Sarah E. ; Thompson, Paul M. ; Hager, Reinmar. / Joint genetic analysis of hippocampal size in mouse and human identifies a novel gene linked to neurodegenerative disease. In: BMC Genomics. 2014 ; Vol. 15, No. 1.
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