Copy Number Variants and Schizophrenia

Approximately 12% of the human genome consists of relatively common copy number variations (CNVs) — i.e., insertions or duplications of DNA sequences (JW Psychiatry Jan 22 2007). Rare CNVs, however, might be associated with some diseases — e.g., autism. Two research groups have now investigated rare CNVs in schizophrenia patients.

Walsh et al. genotyped two study populations. In 150 adults with sporadic or familial schizophrenia, the researchers found a significantly greater risk for rare CNVs than in matched healthy controls. The researchers found an even higher risk for rare CNVs in a group of 83 youths with childhood-onset schizophrenia and no major chromosomal anomalies, compared with 154 of their parents. The frequency of common CNVs did not differ significantly between adult patients and controls. Compared with the rare CNVs found in controls, those in the schizophrenia patients more frequently disrupted gene structure, and these were significantly overrepresented in neurodevelopmental, RNA, and glutamate pathways.

Xu et al. genotyped a sporadic-schizophrenia cohort (152 adults with sporadic schizophrenia and their unaffected parents) and a familial-schizophrenia cohort (48 parent-child trios where a close relative also had schizophrenia). Controls were 159 healthy volunteers from the community and their parents. Again, rare CNVs were significantly more frequent in the schizophrenia cohorts than in the control group and more frequent in the sporadic cohort than in the familial cohort. Some of the rare CNVs were found in unaffected parents in the control and sporadic-schizophrenia groups.