Publication: IDENTIFICATION OF HUMAN GENOMIC VARIATIONS RELATED TO AUTISM SPECTRUM DISORDER (ASD) AND OBESITY IN ASIAN POPULATIONS
Date
2023
Authors
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Publisher
International Medical University
Abstract
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.
Description
Keywords
Autism Spectrum Disorder, Obesity, Genetics, Genes, Mental Disorders