Aim:

The role of common variants in ASC and related endophenotypes can be investigated using genetic association studies. While candidate gene association studies have identified a few variants that have been replicated, the majority of GWAS results have not been replicated (Berg and Geschwind 2012). Possible reasons for the failure of GWAS studies could be: 1) the high clinical and genetic heterogeneity underlying ASC; 2) the need for much larger sample sizes than previously thought; 3) The effect sizes of a single common variant is much smaller than previously thought, suggesting multiple epistasis. One solution to these problems is to test for genetic associations for underlying endophenotypes. Many of the underlying endophenotypes such as attention to detail, systemizing ability and empathy are quantitative traits present in the general population. Individuals with ASC are usually present at one end of the curve of these traits. Understanding which genetic variants, and by extension, which genetic and biological networks contribute to these traits will help us understand, in part, the variants that contribute to ASC. Due to the complex nature of these endophenotypes, a model-free GWAS would be the best approach to understand these traits. These studies must be sufficiently powered and must include a replication sample in order to be reliable. We have a number of different online psychological tests of empathy, attention to detail, systemizing, mathematical ability, and synaesthesia that are sensitive to individual differences in the general population and that are related to the autism phenotype. Many of them have a genetic component and are polygenic. We are interested in identifying the genes that show association with these traits.