The majority of CNV contribution to disease remains unknown. The genetic associations listed in Table 1 consist almost entirely of genomic hotspots (Mefford and Eichler, 2009). These represent the largest and most pathogenic risk alleles. However, in studies of de novo CNV these hotspots represent 25% of mutations and thus, probably represent a minority of the risk variants. The majority are non-recurrent mutations, which have lower mutation rates and lower frequencies and will require larger studies to unequivocally demonstrate an association with disease. Such large scale studies are underway through International efforts including by the Psychiatric Genomics Consortium (PGC) (Ripke et al., 2011) and Wellcome Trust Case Control Consortium (WTCCC). Large Scale meta-analysis of GWAS has obtained statistically convincing evidence for common variants in schizophrenia (Ripke et al., 2011) and bipolar disorder (Sklar et al., 2011). These efforts are accompanied by ongoing CNV studies of the same cohorts, and will be well powered to capture additional risk genes.
