# Estimating the Prevalence and Genetic Risk Mechanisms of ARFID in a Large Autism Cohort

## TL;DR

This study estimates the prevalence of ARFID in an autism cohort and identifies genetic risk factors, suggesting a lifelong risk and a potential genetic link to autism and other traits.

## Contribution

First genetically-informed investigation of ARFID in a large autism cohort, providing prevalence and heritability estimates and a genome-wide association finding.

## Key findings

- ARFID prevalence in the autism cohort is 21%, higher than previous clinical estimates.
- Narrow-sense heritability for ARFID risk is estimated at 0.45.
- A genome-wide association signal near ZSWIM6 was identified, linked to neurodevelopmental conditions.

## Abstract

This study is the first genetically-informed investigation of avoidant/restrictive food intake disorder (ARFID), an eating disorder that profoundly impacts quality of life for those affected. ARFID is highly comorbid with autism, and we provide the first estimate of its prevalence in a large and phenotypically diverse autism cohort (a subsample of the SPARK study, N = 5,157 probands). This estimate, 21% (at a balanced accuracy 80%), is at the upper end of previous estimates from studies based on clinical samples, suggesting under-diagnosis and potentially lack of awareness among caretakers and clinicians. Although some studies suggest a decrease of disordered eating symptoms by age 6, our estimates indicate that up to 17% (at a balanced accuracy 87%) of parents of autistic children are also at heightened risk for ARFID, suggesting a lifelong risk for disordered eating. We were also able to provide the first estimates of narrow-sense heritability (h2) for ARFID risk, at 0.45. Genome-wide association revealed a single hit near ZSWIM6, a gene previously implicated in neurodevelopmental conditions. While, the current sample was not well-powered for GWAS, effect size and heritability estimates allowed us to project the sample sizes necessary to more robustly discover ARFID-linked loci via common variants. Further genetic analysis using polygenic risk scores (PRS) affirmed genetic links to autism as well as neuroticism and metabolic syndrome.