Autism genetics: opportunities and challenges for clinical translation

Key Points A rapidly growing list of rare genetic causes of autism spectrum disorders (ASDs) is being identified, giving insights into the underlying biology of these disorders. Contrary to what is generally assumed, existing genetic findings are already able to inform our current clinical practice. Genetic findings have great potential to improve the quality of health care provided to individuals with an ASD and to improve their quality of life. However, several initiatives are needed to support the translation of this knowledge into health care. It is important to promote the education of the relevant health care professionals about clinical genetic testing and its possible benefits. We must also adopt a broader view of ASDs that recognizes psychiatric and somatic comorbidity. The field would benefit greatly from unprecedented global cooperation to improve sharing of genotype–phenotype data from cross-sectional and longitudinal studies. Furthermore, researchers and clinicians must work in partnership with the autism community regarding the genetics and health care research agenda. Finally, genetic information should be used to develop future treatments and interventions for psychiatric and somatic comorbidity, and should be evaluated in clinical trials. The question is not so much when ASD genetics will start to influence our clinical practice but rather how we can optimally use the knowledge that we already have and what is required to use its full clinical potential in the future. Various large studies have provided unprecedented insights into the genetics of autism spectrum disorders (ASDs). This Review discusses the challenges and opportunities of translating genetic and biological insights into clinical progress for ASDs, in areas including genetic testing, ASD classification, genetic counselling, comorbidities and therapeutics. Genetic studies have revealed the involvement of hundreds of gene variants in autism. Their risk effects are highly variable, and they are frequently related to other conditions besides autism. However, many different variants converge on common biological pathways. These findings indicate that aetiological heterogeneity, variable penetrance and genetic pleiotropy are pervasive characteristics of autism genetics. Although this advancing insight should improve clinical care, at present there is a substantial discrepancy between research knowledge and its clinical application. In this Review, we discuss the current challenges