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Review
. 2022 Apr 15;10(1):53.
doi: 10.1186/s40337-022-00578-x.

How genetic analysis may contribute to the understanding of avoidant/restrictive food intake disorder (ARFID)

Hannah L Kennedy  1 , Lisa Dinkler  2   3 , Martin A Kennedy  4 , Cynthia M Bulik  2   5   6 , Jennifer Jordan  7
Affiliations
Review

How genetic analysis may contribute to the understanding of avoidant/restrictive food intake disorder (ARFID)

Hannah L Kennedy et al. J Eat Disord. .

Abstract

Avoidant/restrictive food intake disorder (ARFID) was introduced in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Unlike anorexia nervosa, ARFID is characterised by avoidant or restricted food intake that is not driven by weight or body shape-related concerns. As with other eating disorders, it is expected that ARFID will have a significant genetic risk component; however, sufficiently large-scale genetic investigations are yet to be performed in this group of patients. This narrative review considers the current literature on the diagnosis, presentation, and course of ARFID, including evidence for different presentations, and identifies fundamental questions about how ARFID might fit into the fluid landscape of other eating and mental disorders. In the absence of large ARFID GWAS, we consider genetic research on related conditions to point to possible features or mechanisms relevant to future ARFID investigations, and discuss the theoretical and clinical implications an ARFID GWAS. An argument for a collaborative approach to recruit ARFID participants for genome-wide association study is presented, as understanding the underlying genomic architecture of ARFID will be a key step in clarifying the biological mechanisms involved, and the development of interventions and treatments for this serious, and often debilitating disorder.

Keywords: Fussy eating; GWAS; Heritability; Psychiatric genetics.

Plain language summary

Avoidant/restrictive food intake disorder (ARFID) can be a severe and debilitating eating disorder, where individuals limit food intake for reasons unrelated to the weight and body image concerns observed in anorexia nervosa. Although genetics is known to play a significant role in other eating disorders such as anorexia nervosa and bulimia nervosa, only one study has investigated the genetic background of ARFID, and this was limited to those with ARFID within an autism cohort. This narrative review describes current knowledge about the clinical characteristics of ARFID and highlights current knowledge gaps, setting the scene for a discussion of how existing research findings about the genetics of related conditions might help guide genetic research about ARFID. A large genome-wide association study (GWAS) is recommended as the first step to addressing some of the fundamental biological questions around ARFID and will lay the framework for development of interventions and treatments that target ARFID at a biological level.

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Conflict of interest statement

None for HK, LD, MK, JJ. CM Bulik reports: Shire (grant recipient, Scientific Advisory Board member); Idorsia (consultant); Lundbeckfonden (grant recipient); Pearson (author, royalty recipient); Equip Health Inc. (Clinical Advisory Board).

Figures

Fig. 1
Fig. 1
Polygenic risk score (PRS) calculation to identify high risk individuals. 1. Disorder-specific GWAS on largest possible sample to identify associated alleles. 2. Derive a polygenic risk score model from the GWAS data, which incorporates associated SNPs weighted for size of effect. 3. The polygenic risk model can be applied to individuals in a target sample (independent of GWAS sample) to calculate a single polygenic risk score (PRS) that reflects genetic propensity to the phenotype. 4. Identify highest risk individuals based on genetic propensity alone, or combine PRS with information on factors such as environment, family history, and clinical measures to improve predictive ability
See this image and copyright information in PMC

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