Tracing Autism Traits in Large Multiplex Families to Identify Endophenotypes of the Broader Autism Phenotype

Families comprising many individuals with Autism Spectrum Disorder(ASD) may carry a dominant predisposing mutation. Our aim was to use rigorous phenotyping of the Broader AutismPhenotype (BAP) in large multiplex ASD families to identify endophenotypesof the BAP for future genetic studies. We evaluated ASD/BAP features using standardised tests and a semi-structured interview to assess social, intellectual, executive and adaptive functioning in 109 individuals, including two large multiplex families (Family A: 30; Family B: 34) and an independent sample of small families (n=45). Our protocol identified four psychological endophenotypesof the BAP that were evident in both samples, and showed high sensitivity (97%) and specificity (82%) for individuals classified with the BAP. The patterns of inheritance of these endophenotypesvaried in the two large families, supportingtheir utility for identifying genes in autism.