As described above, GWAS are designed specifically to detect association of common disease variants (typically with allele frequencies ≥5% in a population) [106]; GWAS have essentially no power to detect multiple rare variants in either the same gene or in different genes (the multiple rare variants hypothesis) [107]. However the ability to detect CNVs is a promising parallel approach, since these polymorphisms appear to exist both in common and rare forms and have been demonstrated to contribute to the manifestation of other psychiatric disorders such as autism [62] and schizophrenia [65]. In addition, rare, highly penetrant CNVs can be detected in a relatively small sample size, as demonstrated by studies of schizophrenia which consisted of about 150 individuals [63, 108].
