TAGC 2020 Poster AOlson 2357B.pdf (723.67 kB)

In silico cholinergic pathway analysis indicates possible role for exogenous choline in modulating sensory processing in autism spectrum disorder

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posted on 20.04.2020 by Audrey Olson, Fuquan Zhang, Hongbao Cao, Ancha Baranova, Margaret Slavin
Sensory processing dysfunction is common in autism spectrum disorder. Sensory processing relies upon sensory gating – ligand-activated, ion-channel-mediated pathways built upon cholinergic signals. Acetylcholine plays roles in sensory processing, including auditory signal pathways, as well as cognitive function, memory, and learning.

Choline, the precursor to acetylcholine, is an essential nutrient that must be consumed from exogenous sources (foods) to meet the body’s needs for acetylcholine production. Rodent models have demonstrated choline deficient diets are associated with lower levels of acetylcholine in the brain and impaired sensory gating function.

Many American children, including a majority of American children with ASD, do not consume recommended levels of dietary choline. Combined, this evidence supports further investigation of the impact of dietary choline intake upon sensory processing in autism.

Gene set enrichment analysis was conducted to identify Gene Ontology database pathways shared between MSig-DB curated cholinergic pathway gene sets (345 genes total) and a set of 53 autism genes identified by meta-analysis of genome-wide association studies. Ontologies associated with both the autism GWAS set and the MSig-DB functional pathway sets were identified using gene ontology association analysis within Pathway Studio (Elsevier). The lists of ontologies assigned to each of these gene sets were trimmed at approximately the lowest 100 p-values (p <0.01), while using a shift in p-value order of magnitude as the final determinant in list cutoff. The gene ontology lists’ respective areas of overlap were identified using Venny. Associated pathways and ontologies were integrated graphically, using Pathway Studio's natural language processing (NLP) platform to both illustrate and model the potential influence of dietary choline deficiency sensory pathways affected in autism.

The analysis from this integrated approach identifies gene ontological overlap between a gene set from an autism genome-wide association study meta-analysis and cholinergic pathway genes from MSig-DB - particularly for areas related to regulation of ion transport. Illustrated graphical relationships founded on Pathway Studio's NLP show these relationships between acetylcholine, ions, and sensory processing domains. Neurotransmitter GABA and receptor GABBR1 are highlighted particularly as part of a chain of relationships dependent upon sufficient acetylcholine supply - and by extension, sufficient dietary choline. This analysis indicates further research into dietary choline's impact upon sensory processing in autism is warranted.

Funding

Influence of Dietary Choline Intake on Sensory Processing Symptoms and Neurotransmitter Levels in Children with Autism Spectrum Disorder. (Egg Nutrition Center)

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2357B

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