Developing a Genotyping Panel for the Diagnosis and Treatment of Gastrointestinal Dysfunction in Autism

Submission note: A thesis submitted in total fulfillment of the degree of Doctor of Philosophy (Microbiology) to the Department of Physiology, Anatomy and Microbiology, School of Life Sciences, College of Science, Health and Engineering, La Trobe University, Victoria, Australia.

Background: Gastrointestinal (GI) dysfunction is a common comorbidity in Autism Spectrum Disorder (ASD) and can lead to a decrease in quality of life. However, GI symptoms are often under-reported in ASD cohorts due to reporting and communication difficulties. A study of genetic biomarkers for GI dysfunction symptoms and pharmacogentic biomarkers for ASD medications also linked with GI dysfunction symptoms was conducted in order to provide further information on the genetic risk for GI dysfunction associated with autism. Methods: A total of sixty participants were recruited, 10 with autism, 21 with GI dysfunction and 29 without autism or GI dysfunction. Buccal cell samples were collected and sequenced using an Illumina Single Nucleotide Polymorphism (SNP) assay and a GI dysfunction questionnaire was utilized. Data from participants with ASD (3,203) and without ASD (6,594) from the USA National Database for Autism Research (NDAR) and 19 full-text articles were also analysed. Results: Participants with ASD predominantly experienced nausea (23%) and abdominal pain (25%), and were at an increased risk of experiencing nausea, diarrhea and painful bowel movements compared to Typical controls. People in the autism group were significantly more likely to express the risk alleles for CYP2C9, SLC6A2, ABCB1, COMT, OXT and PRL SNPs. The autism group also had reduced risk for having the high-risk genotypes for the IL10 SNP. Conclusion: There is tentative support to the relevance of the ABCB1, COMT, CYP2C9, HTR2A, IL10, OXT, PRL, and SLC6A2 SNPs within the ASD population. Our findings indicate that there is potential for these SNPs to be utilized as biomarkers for a genotyping panel for GI dysfunction in ASD.