The Genetics of Autism Spectrum Disorders

In the last 30 years, twin studies have indicated a strong genetic contribution to Autism Spectrum Disorders (ASD). The heritability of ASD is estimated to be 50 %, mostly captured by still unknown common variants. In approximately 10 % of patients with ASD, especially those with intellectual disability, de novo copy number or single nucleotide variants affecting clinically relevant genes for ASD can be identified. Given the function of these genes, it was hypothesized that abnormal synaptic plasticity and failure of neuronal/synaptic homeostasis could increase the risk of ASD. In parallel, abnormal levels of blood serotonin and melatonin were reported in a subset of patients with ASD. These biochemical imbalances could act as risk factors for the sleep/circadian disorders that are often observed in individuals with ASD. Here, we review the main pathways associated with ASD, with a focus on the roles of the synapse and the serotonin-NAS-melatonin pathway in the susceptibility of ASD.