Gene associations with human anxiety (MAGMA)

Anxiety disorders are common and can be debilitating, with effective
treatments remaining hampered by an incomplete understanding of the
underlying genetic etiology. Improvements have been made in understanding
the genetic influences on mouse behavioral models of anxiety, yet it is
unclear the extent to which genes identified in these experimental systems
contribute to genetic variation in human anxiety phenotypes. Leveraging
new and existing large-scale human genome-wide association studies, we
tested whether sets of genes previously identified in mouse anxiety-like
behavior studies contribute to a range of human anxiety disorders. When
tested as individual genes, thirteen mouse-identified genes were
associated with human anxiety phenotypes, suggesting an overlap of
individual genes contributing to both mouse models of anxiety-like
behaviors and human anxiety traits. When genes were tested as sets, we did
identify fourteen significant associations between mouse gene sets and
human anxiety, but the majority of gene sets showed no significant
association with human anxiety phenotypes. These few significant
associations indicate a need to identify and develop more translatable
mouse models by identifying sets of genes that ‘match’ between model
systems and specific human phenotypes of interest. We suggest that
continuing to develop improved behavioral paradigms and finer-scale
experimental data, for instance from individual neuronal subtypes or
cell-type-specific expression data, is likely to improve our understanding
of the genetic etiology and underlying functional changes in anxiety
disorders.