Schizophrenia is a chronic, severe, and disabling brain disorder which has affected people throughout history. Here we employed an integrated research method: imaging genetics combining neuroimaging data and genetics to investigate the effect of risk variants related to schizophrenia on brain network. We were aimed to illuminate the neural mechanism underlying the association between the risk alleles and schizophrenia. First, we chose to investigate the relationship between a candidate gene: MIR137, which was a well-validated gene related to schizophrenia, and a hypothesis-driven endophenotype: hippocampal formation (HF) functional coupling with dorsolateral prefrontal cortex （DLPFC）. Based on resting-state functional MRI data, we found that individuals homozygous for the MIR137 risk allele (TT) showed significantly different DLPFC-HF functional connectivity compared with other individuals. What’s more, DLPFC-HF functional connectivity was negatively correlated with working memory performance in TG group; however, this phenomenon disappeared in TT group. Our findings confirmed the hypothesis that MIR137 impacts DLPFC-HF coupling and its association with working memory capacity. Then, we employed a voxel-wise data-driven method: eigenvector centrality (EC), to investigate the influence of COMT gene which plays a critical role in central dopamine function, on brain network. We found that Val/Val individuals exhibited significantly higher EC in the left parahippocampal cortex compared to the Met carriers. Furthermore, there was a significantly positive correlation between the mean EC of the significant cluster and the 2-back working memory performance. Our findings may provide plausible implications regarding individual differences in the genetic contribution of COMT to brain network and cognition. At last, since schizophrenia is a polygenic and highly heritable disease and previous studies often only focused on specific variants, we applied polygenic risk score (PGRS) combining the effects of more than twenty thousand risk variants related to schizophrenia, and endophenotype to investigate whether these newly identified alleles are associated with the markers of schizophrenia. We found that the PGRS could predict individual n-back working memory and was associated with resting-state DLPFC-HF functional connectivity. Our findings confirmed the polygenic nature of schizophrenia and the association between these newly identified variants and the cogniti...
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