Cluster Analysis of Short Sensory Profile Data Reveals Sensory-Based Subgroups in Autism Spectrum Disorder

Authors

Ariel M Lyons-Warren
Michael F Wangler
Ying-Wooi Wan

Publication Date

10-27-2022

Journal

International Journal of Molecular Sciences

DOI

10.3390/ijms232113030

PMID

36361815

PMCID

PMC9655407

PubMedCentral® Posted Date

10-27-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Humans, Autism Spectrum Disorder, Autistic Disorder, Phenotype, Cluster Analysis, Cohort Studies, neurodevelopmental disorders, human genetics, sensory processing, autism spectrum disorder, phenotypic biomarker

Abstract

Autism spectrum disorder is a common, heterogeneous neurodevelopmental disorder lacking targeted treatments. Additional features include restricted, repetitive patterns of behaviors and differences in sensory processing. We hypothesized that detailed sensory features including modality specific hyper- and hypo-sensitivity could be used to identify clinically recognizable subgroups with unique underlying gene variants. Participants included 378 individuals with a clinical diagnosis of autism spectrum disorder who contributed Short Sensory Profile data assessing the frequency of sensory behaviors and whole genome sequencing results to the Autism Speaks’ MSSNG database. Sensory phenotypes in this cohort were not randomly distributed with 10 patterns describing 43% (162/378) of participants. Cross comparison of two independent cluster analyses on sensory responses identified six distinct sensory-based subgroups. We then characterized subgroups by calculating the percent of patients in each subgroup who had variants with a Combined Annotation Dependent Depletion (CADD) score of 15 or greater in each of 24,896 genes. Each subgroup exhibited a unique pattern of genes with a high frequency of variants. These results support the use of sensory features to identify autism spectrum disorder subgroups with shared genetic variants.