High frequencies of de novo CNVs in bipolar disorder and schizophrenia

While it is known that rare copy-number variants (CNVs) contribute to risk for some neuropsychiatric disorders, the role of CNVs in bipolar disorder is unclear. Here, we reasoned that a contribution of CNVs to mood disorders might be most evident for de novo mutations. We performed a genome-wide analysis of de novo CNVs in a cohort of 788 trios. Diagnoses of offspring included bipolar disorder (n?= 185), schizophrenia (n?= 177), and healthy controls (n?= 426). Frequencies of de novo CNVs were significantly higher in bipolar disorder as compared with controls (OR?= 4.8 1.4,16.0], p?= 0.009). De novo CNVs were particularly enriched among cases with an age at onset younger than 18 (OR?= 6.3 1.7,22.6], p?= 0.006). We also confirmed a significant enrichment of de novo CNVs in schizophrenia (OR?= 5.0 1.5,16.8], p?= 0.007). Our results suggest that rare spontaneous mutations are an important contributor to risk for bipolar disorder and other major neuropsychiatric diseases.