The common variants implicated in microstructural abnormality of first episode and drug-naïve patients with schizophrenia

Abstract

Both post-mortem and neuroimaging studies have identified abnormal white matter (WM) microstructure in patients with schizophrenia. However, its genetic underpinnings and relevant biological pathways remain unclear. In order to unravel the genes and the pathways associated with abnormal WM microstructure in schizophrenia, we recruited 100 first-episode, drug-naïve patients with schizophrenia and 140 matched healthy controls to conduct genome-wide association analysis of fractional anisotropy (FA) value measured using diffusing tensor imaging (DTI), followed by multivariate association study and pathway enrichment analysis. The results showed that one intergenic SNP (rs11901793), which is 20 kb upstream of CXCR7 gene on chromosome 2, was associated with the total mean FA values with genome-wide significance (p = 4.37 × 10-8), and multivariate association analysis identified a strong association between one region-specific SNP (rs10509852), 400 kb upstream of SORCS1 gene on chromosome 10, and the global trait of abnormal WM microstructure (p = 1.89 × 10-7). Furthermore, one pathway that is involved in cell cycle regulation, REACTOME-CHROMOSOME -MAINTENANCE, was significantly enriched by the genes that were identified in our study (p = 1.54 × 10-17). In summary, our study provides suggestive evidence that abnormal WM microstructure in schizophrenia is associated with genes that are likely involved in diverse biological signals and cell-cycle regulation although further replication in a larger independent sample is needed.