Figure 1. Allele frequency and effect size in ASD.
The graph illustrates the relationship of allele frequency to effect size for ASD-related variants. Rare mutations, as expected, have been found to carry larger effects than common variations. Consistent with the broad medical literature, the scale of effects for common alleles implicated in ASD has been quite modest. The linkage (blue) and association (green) sections illustrate the historically divergent approaches to demonstrating the role of rare versus common variation in disease; rare alleles have been expected to show an approximately 1:1 relationship with a given phenotype, often demonstrated via linkage, while common polymorphisms have been expected to show more probabilistic outcomes, typically demonstrated by some type of case-control association design. The shaded area illustrates that the range of effect sizes for rare alleles identified in ASD to date have been broader than those expected for strictly Mendelian disorders, and that association approaches have been necessary to confirm the relationship of genotype to phenotype.