Genetics of Autism: Overview and New Directions

Genetic epidemiology is the study of inherited factors involved in the etiology of a disease or disorder and uses the methods of both medical genetics and clinical epidemiology. In general, genetic epidemiology tries to answer the following four questions: Is the disorder inherited; What phenotype is inherited; How is it inherited or what is the mode of transmission; and What is the nature of the genetic mutation, if any, that gives rise to the disorder? The hope is that by identifying the gene or genes involved in pathophysiology, a much better understanding of the steps from gene product to phenotype will be possible, leading to improvements in diagnosis, an opportunity for thoughtful family planning, and perhaps, most important, to the development of treatments based on an understanding of the biochemistry of the disorder. We review the current knowledge of the genetic epidemiology of autism and the other pervasive developmental disorders (PDDs) and highlight promising new directions. There seems to be widespread agreement that the PDDs are caused, at least in part, by genetic factors. There is also some agreement on the phenotypic boundaries associated with these same genetic factors. However, many points of uncertainty remain, and several methodologic issues need to be resolved before further progress in mapping susceptibility genes is possible. We do not specifically review molecular studies, medical conditions associated with autism, or the broader autism phenotype, as these topics are covered in other papers in this special issue.