Table 3.

Reports dealing with genetics and their major finding

Domains	Reference	Highlighted
Red flags/screening genetics Neurological pathways	Bhattacharya A, 2020 [15]	Some neuropsychiatric disorders tend to be more associated with AN, such as oppositional defiant disorder, attention deficit hyperactivity disorder, anxiety disorders, obsessive compulsiveness, depressive symptoms, and suicidal ideation. Prior to puberty, the impact of genetics on developing an ED is 50% in males and 0% in females; at puberty it increases to 50% in females with puberty. As the insula helps to integrate and regulate autonomic, affective, and sensory systems, researchers proposed a theory of insular dysfunction playing an etiologic role in AN.
Red flags/screening Genetics, neurological pathways	Grammatikopoulou MG, 2023 [22]	Children and adolescents with autoimmune or autoinflammatory diseases are at greater risk (HR: 37%) of developing AN. Juvenile SLE seems to have specific brain-reactive autoantibodies, which are responsible for the development of NP disorders. Twin studies indicated heritability. Brain scans of affected persons and genome-wide association studies pointed to the fact that AN is primarily observed in families with perfectionist, obsessive, and competitive traits.
Red flags/screening Genetics	Breton E, 2022 [23]	Children and adolescents with an autoimmune or autoinflammatory disease, or a family history of such diseases, are at higher risk of ED; ED patients are at higher risk of autoimmune or autoinflammatory diseases. Findings support an overlap between gene pathways related to obesity and AN as for a genetic correlation between AN and traits related to energy metabolism. AN has identified single-nucleotide polymorphisms in EBF transcription factor 1 which influences leptin signaling and the development of the immune system and which are both likely altered in AN.
Red flags/screening Genetics	Sirufo MM, 2022 [24]	AN and autoimmune diseases have common immunopathological pathways.
Red flags/screening Genetics	Barakat S, 2023 [25]	Autoimmune reactions are a risk factor for the development of AN. In adolescents with SLE, steroid-induced alterations in body weight and shape might act as triggers for body image dissatisfaction and consequently for AN. Corticosteroids use is also associated with psychiatric events: anxiety, agitation, psychosis, insomnia, catatonia, depression, mood and cognitive changes, euphoria, depersonalization, delirium, dementia, and hypomania. These can drive the development of AN in adolescents with juvenile lupus.
Genetics	Donato K, 2022 [31]	AN is highly polygenic; many genetic loci may be involved in molecular pathways that lead to AN: serotonergic, dopaminergic and opioid genes. The 5-hydroxytryptamine system, involved in food intake, mood, and body weight regulation, may be altered in the acute illness state of AN. The dopaminergic system, modulating thinking processes, reward, emotional behavior, substance dependence, feeding and motor activity has been demonstrated to be involved in AN. Opioid receptors polymorphism, involved in food intake, reward sensitivity, pain, and vulnerability to addictive disorders are linked to AN.
Genetics	Paolacci S, 2020 [32]	Four genes (CADM1, MGMT, FOXP1, and PTBP2) are likely to be associated to the AN etiology.
Genetics Environment	Steiger H, 2020 [33]	In a study involving 3,495 people with AN, a locus on chromosome 12 had been found associated with AN Swedish hospital records showed that children having a parent with an autoimmune disorder are likely to develop an ED. A degree of in utero stress exposure correlates to ED. AN studies have reported altered methylation of genes regulating expression of alpha-synuclein, dopamine. oxytocin, histone deacetylase and leptin (hormone linked to nutritional status and the immune response).
Genetics	Watson HJ, 2021 [34]	Twin studies suggest a genetic component for eating disorders. Ranging from 16 to 74% for AN. AN had significant positive single-nucleotide polymorphisms with other psychiatric disorders and negative genetic correlations with anthropometric and metabolic traits, such as BMI, leptin, and fasting insulin a positive genetic correlation was observed with cannabis initiation and AN, negative with smoking phenotypes. Altered levels of adiponectin, a hormone that plays a key role in energy homeostasis and appetite regulation, have been observed in patients with AN. Genes CPA3 and GATA2 expression were positively associated with levels of leptin, suggesting a genetic overlap between AN, autoimmune disease, and metabolic function. Gene TACR1 may contribute to AN pathophysiology: it encodes the tachykinin (or neurokinin) 1 receptor which has previously been associated with anxiety and bipolar disorders and may contribute to AN symptom.
Genetics	Huckins LM, 2022 [35]	Sex-specific relationships between AN and anthropometric traits. AN and body fat percentage are more highly genetically correlated among females than males.
Genetics	Levine MP, 2023 [36]	AN demonstrates higher familial aggregation and higher heritability than other ED. In case of parents with an ED, the risk to develop an ED is 3–5 times higher than the general population; females with the mother affected by ED were 1.9–2.3 times more likely to develop ED.
Genetics	Loeb KL, 2020 [37]	Genetic predisposition led to study family-based treatment to prevent AN in adolescents exhibiting signs and symptoms of subclinical AN.