Several major-effect loci due to de novo or inherited CNV also increase the risk for SCZ. These loci display variable expressivity and incomplete penetrance (27, 28), and several are associated with other disorders, including ASD, epilepsy, and intellectual disability (29, 30). The role of large rare CNVs (rare or de novo) in BPD, major depression, substance abuse, obsessive-compulsive disorder (OCD), attention deficit hyperactivitity disorder (ADHD), or anxiety disorders is less clear and, with a few exceptions, have a smaller magnitude of contribution relative to ASD or SCZ. In ADHD, sample sizes have been relatively small, and the greatest signal resides in those with comorbid intellectual disability (31). Studies of parent-child trios in SCZ and BPD (32) have observed odds ratios (ORs) for carrying large rare de novo CNVs of about five for both, although if de novo CNVs <500 kb are considered, the OR is higher, albeit with wide confidence intervals. Similar to ASD, the contribution from de novo events comes mostly from sporadic rather than familial cases, where the rate of de novo CNVs is closer to that of controls.
