Associated genetics and connectomic circuitry in schizophrenia and bipolar disorder

Abstract

Schizophrenia (SCZ) and bipolar disorder (BD) are severe psychiatric conditions that can involve symptoms of psychosis and cognitive dysfunction. The two conditions share symptomatology, neuropathology, and genetic etiology and are thus regularly hypothesized to share underlying biology. Here we examined the effect of their combined genetic liability on brain connectivity from two perspectives. First, we assessed polygenic score (PGS) for SCZ and BD using genotype data from 19,778 healthy subjects from the UK Biobank, and correlated PGS to the structural brain connectome reconstructed using MRI data within the healthy population. Our findings reveal connectivity of brain circuits of superior parietal and posterior cingulate regions to be particularly associated with combined polygenic effects for SCZ and BD, circuitry that overlaps with brain networks involved in disease conditions (r = 0.239, p < 0.001). Second, conducting a genome-wide association study (GWAS) on genotypic and imaging data from the UK Biobank revealed 9 significant genomic loci associated with SCZ-involved circuits and 14 loci associated with BD-involved circuits. Genes related to SCZ/BD-involved circuits are significantly enriched in gene sets previously reported in GWAS for SCZ and BD. Our findings jointly suggest that polygenic liability of SCZ and BD is associated with the microstructural organization of specific brain circuitry involved in both conditions.