A Search for Overlapping Heritable Mechanisms Between Autism and Normal-range Personality Traits

Abstract

Most cases of autism are thought to be primarily caused by the cumulative action of common low-effect variants. In this thesis, we explore the idea that these common variants serve an alternate function in the general population in helping create normal-range diversity of personality traits. We test our hypotheses in the Simons Simplex Collection, a repository of genomic and phenotypic data for over 2,500 families with autism. In particular, we analyze the relationship between autism in the children and personality traits in the parents, including the Broad Autism Phenotype (BAP) traits and technical subject matter interest. We show that the BAP traits have some SNP-based heritability, we find enrichment of autism genes in areas of the genome associated with the BAP traits through a genome-wide association study, and we observe greater inheritance of possible autism-risk genes by autistic offspring from parents with more intense BAP traits. We overcome moderate problems with statistical power by analyzing the effects of SNP aggregates rather than trying to find individually significant associations. Together, these results build a promising framework for a shared genetic basis between autism and autism-related personality traits that can be validated in the future with larger samples.