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

BMC Genomics

Reinmar Hager³  Paul M Thompson⁴  Sarah E Medland⁶  Thomas E Nichols¹  Derrek P Hibar⁷  Jason L Stein⁴  Lu Lu⁵  Robert W Williams²  David G Ashbrook³ 

[1]Department of Statistics & Warwick Manufacturing Group, The University of Warwick, Coventry CV4 7AL, UK

[2]University of Tennessee Health Science Center, Memphis, TN 38163, USA

[3]Computational and Evolutionary Biology, Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK

[4]Department of Neurology, Laboratory of Neuro Imaging, UCLA School of Medicine, Los Angeles, CA 90095-1769, USA

[5]Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, China

[6]Genetic Epidemiology Laboratory, Queensland Institute of Medical Research Berghofer, Brisbane, Australia

[7]Institute for Neuroimaging and Informatics, Imaging Genetics Center, Keck School of Medicine, University of Southern California, 2001 N. Soto Street, Los Angeles, CA 90033, USA

关键词: BXD;    MGST3;    Hippocampus;    Comparative analysis;   

Others  :  1139153
DOI  :  10.1186/1471-2164-15-850

 received in 2014-04-07, accepted in 2014-09-29,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Ashbrook et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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