While de novo CNVs might have a stronger effect size, it is quite plausible that inherited CNVs could also contribute to risk for BD. Notably, inherited CNVs detected in this study included variants at loci that have been previously linked to schizophrenia (International Schizophrenia Consortium, 2008 and Stefansson et al., 2008), including a duplication at 1q21.1 in a subject with bipolar disorder and a duplication and a deletion at 15q13.3 detected in subjects with bipolar disorder and schizophrenia, respectively (Document S2, bed file). Therefore, we examined the burden of rare inherited CNVs overlapping with genes in BD, SCZ, and controls, and subjects were stratified based on family history. We observed a trend of enrichment for large (≥500 kb) inherited duplications in familial cases of bipolar disorder (OR = 1.77, p = 0.03, Table 3). We did not observe an enrichment of deletions in familial bipolar disorder. Likewise, we did not observe a significant enrichment of deletions or duplications in sporadic bipolar disorder or in schizophrenia (Table 3). These results are consistent with a role for inherited CNVs in familial BD, particularly for large duplications; however, data from a much larger sample are needed to draw firm conclusions.
