Association Between Copy-Number Variations and Savant Skills Among People with Autism Spectrum Disorder

Background: Savant skills, which are defined as “outstanding skills in individuals with otherwise intellectual impairment,” are significantly more common in individuals with autism spectrum disorders (ASD) than in any other group of people examined to date. The existence of such a considerable and well-defined group of extremely talented people within the autism spectrum suggests common underlying mechanisms that require further exploration. We hypothesized that copy-number variations (CNVs), which are thought to play a role in ASD susceptibility, may also underlie these exceptional skills among people with ASD.

Objectives: To study the association between CNVs and savant skills among individuals with ASD.

Methods: We studied 1108 children diagnosed with ASD from the Simons Simplex Collection (SSC) database. Savant skills were determined based on five designated questions regarding exceptional talent in visuospatial ability, memory ability, musical ability, drawing ability, and computational ability from the autism diagnostic interview revised (ADI-R) questionnaire. CNV data were retrieved from a genome-wide analysis of CNV in these children.

Results: Of the 1108 children with ASD in this study, 467 (42%) had one or more savant skills. This prevalence is significantly higher than the observed 31% of savant skills among children with ASD that did not undergo CNV analysis in the SSC cohort (P<0.001). It is also higher than the typically 10%-30% reported prevalence of savant skills among children with ASD in other studies. Similarly to other reports, savant skills in our study were associated with a higher IQ (93.0±24.2 vs. 79.1±25.5; P<0.001), and a larger head circumference (HC) (54.3±2.55 vs. 53.8±2.60; P = 0.003) among children with ASD. Interestingly, we found association between savant skills and a lower count of rare CNVs among children with ASD (14.0±5.54 vs. 14.8±6.2 for children with and without savant skills respectively; P = 0.03). This association mainly reflected differences in copy-number deletions, rather than copy-number duplications, and was particularly noticeable among children with exceptional computational ability (9.1±4.61 vs. 10.1±4.97; P= 0.02) even after accounting for their higher IQ and larger HC. We also examined whether certain talents are predisposed by specific ASD susceptibility CNV loci, but no such associations were found.

Conclusions:

Our findings suggest that CNVs contribute to the presentation of exceptional talents among children with ASD.