Theses (MSc. Molecular Medicine)

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder caused by genetic and/or environmental factors. Several studies have suggested that individuals with ASD may be at an increased risk of obesity. However, whether and how these two disorders are causally linked remains uncertain. Here, we investigate ASD- and obesity-related genetic polymorphisms that were retrieved from multiple publicly available databases. Analysis of human genomic variants associated with ASD and obesity was performed using several bioinformatics approaches (i.e., FUMA, MAGMA, and SNiPA). This study identified a total of 128 SNPs significantly associated with ASD in the European datasets, while 427 SNPs (Asians) and 2,209 SNPs (Europeans) were associated with obesity alone at a genome-wide level. However, we found no such association with ASD in the Asian datasets. At genome-wide suggestive significance level (p < 1.0 x 10-4), rs2535629 (ITIH3) and rs9891146 (C17orf58) were identified to be associated with both disorders in the European datasets. The top lead SNP for ASD and obesity in the Asian datasets were rs10858046 (PKMP1; p = 3.80 x 10-7) and rs10965248 (CDKN2B-AS1; p = 1.10 x 10-98), respectively. Interestingly, 57 obesity-related SNPs were significant at a genome-wide level in both datasets, from which two sentinel SNPs, namely rs2237897 (KCNQ1; p = 2.08 × 10-246) and rs1421085 (FTO; p = 2.40 × 10-245), were also significantly associated with obesity in the Asian and European datasets respectively. In Asian datasets, KCNQ1 was the top significant gene associated with obesity only, while no significant association was found for any known genes with ASD. Gene set enrichment analysis (GSEA) revealed two (Asians) and ten (Europeans) GO terms that were significantly associated with obesity. However, no significant results were found for ASD in both Asian and European populations in the GSEA. These findings raise intriguing questions regarding the biological processes between ASD and obesity. Design of treatment strategies for complex conditions,such as ASD, would benefit from enhanced understanding of underlying psychological/behavioural components in the general population.