title: Joint genetic analysis of hippocampal size in mouse and human identifies a novel gene linked to neurodegenerative disease.
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.
authors.affiliation: Computational and Evolutionary Biology, Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK. david.ashbrook@postgrad.manchester.ac.uk.
authors.forename: David G
authors.initials: DG
authors.lastname: Ashbrook
authors.forename: Robert W
authors.initials: RW
authors.lastname: Williams
authors.forename: Lu
authors.initials: L
authors.lastname: Lu
authors.forename: Jason L
authors.initials: JL
authors.lastname: Stein
authors.forename: Derrek P
authors.initials: DP
authors.lastname: Hibar
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Nichols
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Medland
authors.forename: Paul M
authors.initials: PM
authors.lastname: Thompson
authors.forename: Reinmar
authors.initials: R
authors.lastname: Hager
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D015342:DNA Probes / Q000378:metabolism; D055106:Genome-Wide Association Study; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D019636:Neurodegenerative Diseases / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D040641:Quantitative Trait Loci; D011859:Radiography
chemical_list: D015342:DNA Probes; D005982:Glutathione Transferase