Mapping a shared genetic basis for neurodevelopmental disorders

Abstract

Distinct neurodevelopmental disorders have a common genetic etiology that explains the high degree of comorbidity among these disorders. A recent study sought to identify copy number variants across five neurodevelopmental disorders, and detected an enrichment for chromosome 9p24.3 duplication encompassing DOCK8 and KANK1 in affected individuals. Such large-scale studies will help uncover additional causative and modifier loci within common pathways, which will enable the development of therapeutic targets for the treatment of multiple disorders.See related research 10.1186/s13073-017-0494-1.

Keywords: Causative variants; Complex disease; Copy number variants; Gene discovery; Modifiers; Neurodevelopmental disorders.

Fig. 1

Shared genetic etiology in neurodevelopmental disorders. a Venn diagram showing associations for 16 rare pathogenic copy number variants (CNVs) identified in disease cohorts for four neurodevelopmental disorders: intellectual disability/developmental delay (ID/DD) [4], autism [5], schizophrenia [6], and epilepsy [7]. Odds ratios for each disorder were calculated for each CNV based on the study data, with an odds ratio > 2 used to assign a CNV to a particular neurodevelopmental disorder. The grey scale bars next to the highlighted CNVs represent odds ratios (in order from left to right) for intellectual disability, autism, schizophrenia, and epilepsy. b Venn diagram showing associations for 242 genes with at least one identified de novo loss-of-function variant or single-gene deletion found in neurodevelopmental disease cohorts [10]. c A model for the contributions of genetic variants with different effect sizes towards various neurodevelopmental disorders. Variants with larger effect sizes are likely to be primary causal variants, while variants with smaller effect sizes indicate modifiers that modulate the phenotype in concert with other variants