A population-based twin-study of autism spectrum disorders: genetic and environmental sources of cognitive and clinical

Autism is a devastating disorder affecting the ability to make social relationships, communicate and break out of rigid routines. Autism and autism spectrum disorders (ASD) affect over 500,000 families in the UK. While ASD is known to be heritable, the exact genes involved are not known. Similarly, despite much public concern, no environmental risk factors have been discovered. We aim to establish the largest twin study of ASD to date, within an existing study of all twins born in England and Wales in 1994-1996. We would assess twins with state-of-the-art diagnostic tools, and give tests for psychological strengths and weaknesses, as well as asking parents about possible environmental factors. Comparing identical and fraternal twins, and looking at the relationships between diagnosis, symptoms, and psychological and environmental measures, will identify possible subgroups within the autism spectrum. This work should speed the identification of genetic and environmental factors that, perhaps in interaction, predispose a child to autism. Discovering these factors is the first step in providing intervention and treatment for autism spectrum disorders.

Progress in understanding the causes of and possible treatments for autism has been hampered by the heterogeneous nature of autism spectrum disorders (ASD). Autism is among the most heritable of psychiatric disorders, yet little progress has been made identifying genes, perhaps due to genetic heterogeneity within ASD. At the same time, lack of perfect concordance, plus a perception of rise in prevalence of ASD, has raised concern regarding possible environmental risk factors. We aim to investigate genetic and environmental sources of heterogeneity within ASD. The proposed project would establish the largest population-based twin sample of the full autism spectrum, with contemporaneous prospective developmental data, within a large normative sample. We propose to assess up to 200 ASD twin pairs and 100 comparison pairs (including IQ-matched controls) using gold-standard diagnostic assessments, a comprehensive cognitive battery, and targeted questions about putative environmental risk factors. With more than twice the sample size in existing published twin studies of ASD, we will have power to investigate; a) genetic subtypes/familial aspects of the phenotype for directed linkage and association studies; b) independence/unity of different symptom/cognitive domains within ASD; c) candidate environmental factors in relation to genetic vulnerability.