Background: Increasing evidence supports the significance of copy number variants (CNVs) – chromosomal regions of ≥1000kb of duplications/deletions – in the genetic contribution to psychiatric illnesses, particularly schizophrenia (SCZ). This study utilizes a robust approach to uncovering genetic variants within the heterogeneity of SCZ by delineating correlations between CNV data and extensive phenotypic data in SCZ patients.

Methods: Phenotypic and CNV data of 348 SCZ patients were collected from medical history records and Affymetrix SNP Array 6.0 assay, respectively. The number of autosomal, X-linked and total CNV counts were plotted against SCZ severity scores, age of onset, number of concurrent psychiatric diagnoses, psychiatric illnesses in family history, and non-psychiatric phenotypes. T-tests and one-way ANOVA were performed among the various categories to identify significant associations.

Results: Increasing numbers of X-linked, autosomal, and total CNVs were found to be significantly associated with suicide attempt in SCZ patients, suicide attempt in family history of SCZ patients, as well as incidence of head injury in SCZ patients. Burdens of X-linked and autosomal CNVs, were found to be associated with history of substance abuse in family members of patients (p=0.014 and p=0.015, respectively). The number of X-linked CNVs, specifically gains/duplications (p=0.040), were significantly associated with digestive system disorders, within the patient sample. Number of concurrent diagnoses was also associated with number of psychiatric illnesses in the family history, and with earlier SCZ age of onset.

Conclusions: These results suggest a strong association between CNVs burdens and specific phenotypic presentations in the SCZ patient population. This is compatible with the ever-increasing number of micro-deletion and micro-duplications found to be associated with neurodevelopmental disorders and our findings may contribute to expanding the neuropsychiatric phenotypes associated with these genetic variants. A particularly interesting finding was the association of CNV burden with incidence of head injury within the person’s life-time, which provides an initial pointer to potential, specific environmental factors that may have a contributory role in schizophrenia. Further analyses will be undertaken to define specific CNVs and genes contained within the affected regions to better characterize potential effects on the phenotypic presentation of SCZ patients.