In a study in which scientists took a novel approach to deciphering the genetics of autism, scientists have found that autism has a high degree of heritability, and have revealed new genetic characteristics that underlie the disorder. The researchers also determined that dysfunctions and delays in language skills are likely a core feature of autism. The findings have been reported in the Proceedings of the National Academy of Sciences (PNAS).
In previous studies that have investigated potential genetic contributions to the development of autism spectrum disorder (ASD), scientists have tended to focus on families in which only one child is affected by the developmental disorder, and have often omitted families that have multiple affected children. As such, primarily rare genetic variants that can contribute to autism have been found; in this work, the researchers contend that this methodlogy has excluded more common genetic variants that are influencing ASD development.
"Study design is critical and not enough attention has been paid to studying families with more than one affected child," said lead study author Dr. Daniel Geschwind, a Distinguished Professor at UCLA.
In this study, the researchers sequenced the genomes of 4,551 people in 1,004 families in which two or more children had ASD; the genomes of 1,836 affected children and 418 neurotypical children were sequenced. This showed that there could be seven genes that are contributing to ASD risk: FBXL13, PLEKHA8, PRR25, SLFN5, SNCAIP, TGM1, and VPS54.
This study has also shown that children who inherit a high level of rare variants or genetic mutations from their parents can have an increased risk of ASD. This may explain why parents might not have symptoms of ASD while their children do, and that there could be a particular genetic 'threshold' of mutations or variants that must be met before ASD is observed.
The investigators also determined that when children exhibit language delays, they are more likely to have a higher genetic risk of ASD, or a polygenic score that has ben linked to ASD. This genetic pattern is not seen in other psychological traits such as bipolar disorder or schizophrenia. The researchers suggested that this may indicate a strong connection between language delay and the genetic component of ASD risk.
Right now, language delays are not considered to be a core symptom of ASD, according to the the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5), in part because the language abilities of these patients are highly variable from one individual to another.
"This association of general risk for ASD that was strongest in those with language delay suggests that language is actually a core component of ASD. This finding needs to be replicated in larger cohorts, especially those recruited more recently under DSM-5," Geschwind added.