Two previous case-control studies have observed an enrichment of rare CNVs in bipolar disorder and in subjects with an early age at onset. However, the observed effects were small (OR ~ 1.3) and results from two other studies (Grozeva et al., 2010 and McQuillin et al., 2011) did not support these findings. In our present study, which focused on the detection of de novo CNVs using a family-based design, we observe a large effect (OR > 4). This is consistent with other family-based studies of autism (Levy et al., 2011, Marshall et al., 2008, Sanders et al., 2011 and Sebat et al., 2007) and schizophrenia (Xu et al., 2008 and Xu et al., 2009) that have found a strong and robust genetic effect for de novo mutations and a weaker genetic effect for inherited variants. The much greater effect size for de novo CNVs as compared with inherited variants is consistent with de novo mutations having a much higher proportion of risk alleles relative to neutral alleles.
