Phenotypic and Genotypic Heterogeneity in Autism Spectrum Disorder

Caitlin C Clements, University of Pennsylvania


Many genetic events can cause autism spectrum disorder (ASD). One specific genetic event involves deletion or duplication of approximately 50 genes, 22q11.2 Deletion/Duplication Syndrome, and leads to ASD in 10-40% of cases. Chapter 1 describes an effort to identify a critical region that confers ASD risk within those ~50 genes and reports that the Low Copy Repeat-A to B region shows the strongest association. Next, we explore ‘background genetics’ the remainder of the genome, almost entirely inherited from one’s parents - that interact with genetic events such as 22q11.2 deletions/duplications. Quantifying a heritable phenotype in one’s parents can indirectly quantify the phenotype encoded in one’s ‘background genetics.’ Heterogeneity among individuals with 22q11.2 Deletion/Duplication Syndrome, therefore, can be partially explained by heterogeneity among their parents’ phenotypes. An ideal heritable trait in which to explore this framework is one of the most studied and understood constructs in psychology: IQ. However, few studies measure parental IQ due to the prohibitive cost and inconvenience of current IQ assessments. Chapter 2 reports the optimal methods for using small sample sizes to develop and calibrate a large, computer adaptive item pool for a new IQ assessment. The method described can be used to develop an online IQ test to facilitate data collection from families and understanding of ‘background genetics.’ Chapter 3 tests whether ‘IQ’ holds the same meaning for children with autism when assessed with the Differential Ability Scales, 2nd Edition (DAS-II) compared to the normative, standardization sample and reports that while verbal and nonverbal reasoning scores do function similarly between groups, the spatial composite score does not. Taken together, these three chapters advance our understanding of IQ assessment in autism and provide one example of a genetics-first sample in which these insights can be applied. Given the importance of IQ for predicting outcomes and its heterogeneity within genetically homogenous samples, the rapidly evolving field of ASD behavioral genetics stands to benefit from an efficient, valid online IQ assessment of verbal and nonverbal reasoning, which hold the same meaning for individuals with autism and typical individuals on the commonly used DAS-II.

Subject Area

Psychology|Mental health

Recommended Citation

Clements, Caitlin C, "Phenotypic and Genotypic Heterogeneity in Autism Spectrum Disorder" (2020). Dissertations available from ProQuest. AAI28026306.