De novo and inherited CNVs in MZ twin pairs selected for discordance and concordance on Attention Problems

Copy number variations (CNVs) have been reported to be causal suspects in a variety of psychopathologic traits. We investigate whether de novo and/or inherited CNVs contribute to the risk for Attention Problems (APs) in children. Based on longitudinal phenotyping, 50 concordant and discordant monozygotic (MZ) twin pairs were selected from a sample of 3200 MZ pairs. Two types of de novo CNVs were investigated: (1) CNVs shared by both MZ twins, but not inherited (pre-twinning de novo CNVs), which were detected by comparing copy number (CN) calls between parents and twins and (2) CNVs not shared by co-twins (post-twinning de novo CNVs), which were investigated by comparing the CN calls within MZ pairs. The association between the overall CNV burden and AP was also investigated for CNVs genome-wide, CNVs within genes and CNVs outside of genes. Two de novo CNVs were identified and validated using quantitative PCR: a pre-twinning de novo duplication in a concordant-unaffected twin pair and a post-twinning deletion in the higher scoring twin from a concordant-affected pair. For the overall CNV burden analyses, affected individuals had significantly larger CNVs that overlapped with genes than unaffected individuals (P0.008). This study suggests that the presence of larger CNVs may increase the risk for AP, because they are more likely to affect genes, and confirms that MZ twins are not always genetically identical. © 2012 Macmillan Publishers Limited. All rights reserved.