Anorexia nervosa (AN) is a complex multi-factorial disease with high heritability.
The psychological AN symptoms are poorly connected with specific molecular mechanisms.
Here we review the molecular basis of AN with the focus on human genetic association
studies; we put these in the experimental biological context with emphasis on molecular
systems controlling food intake and body weight in a direct or indirect manner. We
systematically searched for human genetic studies related to AN and grouped data into
main categories/systems reflecting their major known roles: (1) Systems related to
mental disorders (serotonin, brain-derived neurotrophic factor (BDNF), norepinephrine
(NE), glutamate (NMDA) receptor and SK3 channel, KCCN3). (2) Hunger regulatory systems
(leptin, AGRP, MSH, melanocortin 4 receptor (MC4R), NPY, ghrelin, cholecystokinin
(CCK). (3) Feeding motivation- and reward-related systems (opioids, OPRD1, cannabinoids
(anandamide (AEA), THC, CBR1), dopamine, DRD2, DRD3, DRD4, catecholamine-O-methyl
transferase (COMT). (4) Systems regulating energy metabolism (uncoupling proteins
2 and 3 (UCP2 and UCP3). (5) Neuroendocrine systems with emphasis on sex hormones
(estrogen receptor-beta (ESR2). (6) The immune system and inflammatory response (tumor
necrosis factor-alpha (TNF-alpha)). Overall, we found that in total 175 association
studies have been performed on AN cohorts on 128 different polymorphisms related to
43 genes. We review the strongest associations, identify some genes that have an important
role in regulating BMI whose possible relationship to AN has not been investigated
and discuss the potential targets for pharmacological interventions.