Common risk alleles for schizophrenia within the Major Histocompatibility Complex predict white matter microstructure

Abstract Recent research has highlighted the role of complement genes in shaping the microstructure of the brain during early development, and in contributing to common allele risk for Schizophrenia. We hypothesised that common risk variants for schizophrenia within complement genes will associate with structural changes in white matter microstructure within tracts innervating the frontal lobe. Our results show that risk alleles within the complement gene set, but also intergenic alleles, significantly predict axonal density in these white matter tracts. More specifically, risk alleles within the Major Histocompatibility Complex (MHC) region in chromosome 6 appeared to drive these association, although intergenic alleles mostly within chromosome 19 also show to play part. No significant associations were found for the orientation dispersion index. Our results suggest changes in axonal packing - but not in axonal coherence - determined by common risk alleles within the MHC genomic region, as a potential neurobiological mechanism for schizophrenia.