Association of rs1059004 polymorphism in the OLIG2 locus with whole-brain functional connectivity in first-episode schizophrenia

Abstract

The rs1059004 in the oligodendrocyte lineage transcription factor 2 (OLIG2) gene has been reported to be a candidate single nucleotide polymorphism (SNP) for schizophrenia (SZ). A variety of functional magnetic resonance imaging (fMRI) studies have revealed disconnection in SZ. We aimed to investigate the association of rs1059004 polymorphism with whole-brain functional connectivity (FC) and to further explore the correlation between altered FC and cognitive behavioral scales. Fifty-five SZ patients and fifty-three matched healthy controls were included in this study. The general linear model was used to test the role of rs1059004 polymorphism in whole-brain FC based on resting-state fMRI. Spearman’s rank correlation test was used to calculate the correlation coefficient between FC strength and behavior score. In the whole-brain FC analysis, we found that the FC pattern in SZ patients differs from healthy controls. Furthermore, compared to homozygous C carriers, risk A allele carriers have reduced FC strength in both SZ patients and healthy controls. For the correlation analysis in risk A allele carriers, we found a positive correlation between FC strength and verbal fluency score in SZ patients, while healthy controls appeared to have the opposite result. Our results revealed that participants carrying the risk A allele show FC patterns differing from those of homozygous C carriers. This result suggests that rs1059004 polymorphism and SZ have synergistic effects on brain connections. The correlation analysis result suggests that special attention should be paid to SZ patients who carry the risk A allele because the patients perform worse in verbal fluency.