Associations between polygenic risk scores and amplitude of low-frequency fluctuation of inferior frontal gyrus in schizophrenia

Abstract

Schizophrenia (SCZ) is a serious and complex mental disorder with high heritability. Polygenic risk score (PRS) is a useful tool calculating the accumulating effects of multiple common genetic variants of schizophrenia. The amplitude of low-frequency fluctuation (ALFF) is an efficient index to reflect spontaneous, intrinsic neuronal activity. Aberrant ALFF of brain regions were reported in schizophrenia frequently, but the relationship between PRS and ALFF has not been studied. In the present study, we compared PRS and ALFF in 101 schizophrenia patients and 106 age-matched healthy controls to test their associations with schizophrenia. Then, the correlation of PRS with ALFF was measured to reveal the effect of polygenic risk on brain activity in schizophrenia. We found that schizophrenia patients showed significant differences in PRS and ALFF compared with controls. Twenty-six brain regions showed significant difference of ALFF between schizophrenia cases and controls, of which left inferior frontal gyrus, triangular part (IFGtriang.L) showed increased activity in schizophrenia. PRS-SCZ was positively correlated with ALFF in IFGtriang.L in 57 non-chronic patients. Genes involved in synaptic organization and transmission, especially in glutamatergic synapse, were highly enriched in PRS-SCZ genes, suggesting the dysfunction of synapses in schizophrenia. These results help to understand the molecular mechanism underlying schizophrenia and related brain dysfunction.

Keywords: Amplitude of low-frequency fluctuation; Polygenic risk score; Resting-state functional magnetic resonance imaging; Schizophrenia.