Copy Number Variation Analysis of 100 Twin Pairs Enriched for Neurodevelopmental Disorders

Hundreds of penetrant risk loci have been identified across different neurodevelopmental disorders (NDDs), and these often involve rare (<1% frequency) copy number variations (CNVs), which can involve one or more genes. Monozygotic (MZ) twin pairs are long thought to share 100% of their genomic information. However, genetic differences in the form of postzygotic somatic variants have been reported recently both in typically developing (TD) and in clinically discordant MZ pairs. Here, we sought to investigate the contribution of CNVs in 100 twin pairs enriched for NDD phenotypes with a particular focus on MZ pairs discordant for autism spectrum disorder (ASD) using the PsychChip array. In our collection, no postzygotic de novo CNVs were found in 55 MZ twin pairs, including the 13 pairs discordant for ASD. When analyzing the burden of rare CNVs among pairs concordant and discordant for ASD/NDD in comparison with typically developed (TD) pairs, no differences were found. However, we did detect a higher rate of CNVs overlapping genes involved in disorders of the nervous system in MZ pairs discordant and concordant for ASD in comparison with TD pairs (p=0.02). Our results are in concordance with earlier findings that postzygotic de novo CNV events are typically rare in genomic DNA derived from saliva or blood and, in the majority of MZ twins, do not explain the discordance of NDDs. Still, studies investigating postzygotic variation in MZ discordant twins using DNA from different tissues and single cells and higher resolution genomics are needed in the future.