Etiology of the Broad Avoidant Restrictive Food Intake Disorder Phenotype in Swedish Twins Aged 6 to 12 Years

Abstract

Importance: Avoidant restrictive food intake disorder (ARFID) is characterized by an extremely limited range and/or amount of food eaten, resulting in the persistent failure to meet nutritional and/or energy needs. Its etiology is poorly understood, and knowledge of genetic and environmental contributions to ARFID is needed to guide future research.

Objective: To estimate the extent to which genetic and environmental factors contribute to the liability to the broad ARFID phenotype.

Design, setting, and participants: This nationwide Swedish twin study includes 16 951 twin pairs born between 1992 and 2010 whose parents participated in the Child and Adolescent Twin Study in Sweden (CATSS) at twin age 9 or 12 years. CATSS was linked to the National Patient Register (NPR) and the Prescribed Drug Register (PDR). Data were collected from July 2004 to April 2020, and data were analyzed from October 2021 to October 2022.

Main outcomes and measures: From CATSS, NPR, and PDR, all parent reports, diagnoses, procedures, and prescribed drugs that were relevant to the DSM-5 ARFID criteria were extracted when twin pairs were aged 6 to 12 years and integrated into a composite measure for the ARFID phenotype (ie, avoidant/restrictive eating with clinically significant impact, such as low weight or nutritional deficiency, and with fear of weight gain as an exclusion). In sensitivity analyses, autism and medical conditions that could account for the eating disturbance were controlled for. Univariate liability threshold models were fitted to estimate the relative contribution of genetic and environmental variation to the liability to the ARFID phenotype.

Results: Of 33 902 included children, 17 151 (50.6%) were male. A total of 682 children (2.0%) with the ARFID phenotype were identified. The heritability of ARFID was 0.79 (95% CI, 0.70-0.85), with significant contributions from nonshared environmental factors (0.21; 95% CI, 0.15-0.30). Heritability was very similar when excluding children with autism (0.77; 95% CI, 0.67-0.84) or medical illnesses that could account for the eating disturbance (0.79; 95% CI, 0.70-0.86).

Conclusions and relevance: Prevalence and sex distribution of the broad ARFID phenotype were similar to previous studies, supporting the use of existing epidemiological data to identify children with ARFID. This study of the estimated genetic and environmental etiology of ARFID suggests that ARFID is highly heritable, encouraging future twin and molecular genetic studies.

Figure.. Identification of the Avoidant Restrictive Food Intake Disorder (ARFID) Phenotype Between Age 6 and 12 Years Among 33 902 Twins

Diagnoses, procedures, and prescribed drugs between age 6 and 12 years were included. A-TAC indicates Autism-Tics, AD/HD, and Other Comorbidities Inventory; ATC, Anatomical Therapeutic Chemical Classification System; BMI, body mass index; ICD-10, International Statistical Classification of Diseases and Related Health Problems, Tenth Revision. ^aVariables are parent reported at age 9 or 12 years. ^bThree individuals received a diagnosis of anorexia nervosa (ICD-10 codes F50.0 or F50.1; 1 individual received both codes) between age 6 and 12 years. Age at first diagnosis was around 11 years and 8 to 9 months for all 3 individuals. One individual was excluded in the next step (ie, did not meet DSM-5 ARFID criteria A and C) because of parent-reported fear of weight gain. ^cTen individuals who met ARFID criterion A were removed because of missing response on this item. ^dDiagnostic codes for medical conditions that could potentially exclude an ARFID diagnosis were selected based on their presence in the sample; therefore, not all medical conditions that could potentially be an exclusion criterion for ARFID are listed here.