IBD Mapping of Autism Microarray Data - Beyond Linkage and Association Mapping

Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders including autistic disorder, Asperger's syndrome, and pervasive developmental disorder- not otherwise specified (PDD-NOS). ASD patients are characterized by a qualitative impairment in social interaction as well as restricted repetitive and stereotyped patterns of behavior, interests, and activities. There are several factors that support a genetic component in the etiology of ASDs, like evidence from twin studies and a relatively high recurrence risk for siblings. An association with ASD has been reported for more than 3000 genes, but for most affected individuals the underlying genetic factors have not been found yet. ldentity by descent (IBD) between two individuals means that their alleles are identical because they were inherited from a common ancestor. This information can be used via IBD mapping to increase the power of association analysis by grouping single nucleotide variants (SNVs) based on IBD. The basic principle of IBD mapping is to look for segments of DNA that are shared identical by descent more often among cases than controls. For the purpose of this thesis two different IBD detection methods, namely PLINK and HapFABIA, have been applied to a single nucleotide polymorphism (SNP) microarray dataset from the Autism Genetic Resource Exchange (AGRE). The aim was to use IBD mapping to find part of the missing heritability of autism. HapFABIA has not been used on microarray data before, therefore another goal was to see whether the method works on these kind of data and which settings need to be used. Although no significant findings remained after correction for multiple testing, some IBD segments that were found with HapFABIA indicated the presence of increased sharing among cases and could be mapped to genes that have been previously associated with ASD. Further analyses are needed to confirm or dismiss the results of this thesis.