RGMA in brain showed the rs12442183*T risk allele to be associated with higher expression of RGMA transcript variant 4 (encoding RGMa isoform 3) in frontal cortex. This observation is consistent with the upregulation of Rgma in C57BL/J6 mice treated with morphine chronically, which is not the case in three other mouse strains: DBA/2J, 129P3/J and SWR/J. C57BL/6J mice have a greater preference for oral self-administration of morphine than three other strains (19). Further co-expression analysis in large brain tissue expression datasets demonstrated significant correlation between the expression of RGMA and that of four genes that have been shown to affect risk for other psychiatric disorders, GRIN1 (schizophrenia) (23), KCNIP3 (Alzheimer's disease) (25), FXYD6 (schizophrenia) (21) and PTCHD1 (autism) (26), as well as two transcription factors TCF3 and TCF4. The latter gene TCF4 is a schizophrenia-risk gene (28). These RGMA co-expressed genes are critical to normal brain function, supporting the potential involvement of RGMA in related biological processes.
