Variation due to CNVs arises from a combination of rare and common alleles; as with SNPs most variants are rare but most of the differences between any two individuals arise from a limited set of common (MAF ≥ 5%) copy number polymorphisms (CNPs)55. Disease-associated CNVs detected so far, like disease-associated SNPs, include rare variants with large associated effect sizes, and common variants with more modest effects but carried by a large proportion of the population (Table 2). An added twist is that rare, highly penetrant CNVs have generally been large (600 kb–3 mega-bases (Mb), affecting many genes), whereas disease-associated common CNPs have been much smaller (20–45 kb) and have identified specific genomic features for follow-up study. Because both rare and common CNVs are under-ascertained by current methods, the relative affect of these variants will continue to be an important research question for CNVs just as for SNPs. Of note, CNVs arising de novo in current cases and shown to be of importance in neuropsychiatric and developmental conditions56–58 will not contribute to family resemblance and heritability, but could explain some of the variation at present attributed to ‘environment’.
