Complex segregation analysis of autism

A complex segregation analysis of autism in 185 Utah families was carried out using the mixed model. The 209 affected individuals in these families represent nearly complete ascertainment of the autistic cases born in Utah between 1965 and 1984. The sibling recurrence risk for autism was 4.5% (95% confidence limits 2.8%-6.2%). Likelihoods were maximized for major-gene models, a polygenic model, a sibling-effect model, and a mixed model consisting of major-gene and shared-sibling effects. The analysis provided no evidence for major-locus inheritance of autism. Subdivision of the sample according to the probands' IQ levels showed that sibling recurrence risk did not vary consistently with IQ level. A segregation analysis of families in which the proband had an IQ less than 50 also failed to provide evidence for a major locus. However, because of the etiologic heterogeneity of this disorder, genetic analysis of other meaningful subsets of families could prove informative.