Research has implicated new genetic variants in the risk of developing the common eating disorders anorexia and bulimia.
Anorexia nervosa and bulimia nervosa are severe and relatively common eating disorders (EDs) characterised by distorted body image and abnormal eating patterns, with among the highest mortality rates of all mental health conditions. Genetic factors are thought to be important in disease risk, with estimates of total genetic risk controbution ranging from 50 to 80%, but there has been limited success in identifying specific genes that may be involved.
A new study published in the Journal of Clinical Investigation examined two families with multiple affected family members across several generations using whole genome sequencing, and found that they shared mutations in one of two genes that were not present in unaffected family members.
The ESRRA gene encodes the transcription factor estrogen-related receptor a, which is known to be involved in energy balance and is influenced by external factors such as exercise or calorie restriction. The HDAC4 gene produces the transcriptional repressor histone deacetylase 4, which has been implicated in processes relevant to EDs including exercise and body weight maintenance.
Researchers found that the two proteins interact, with HDAC4 repressing the activities of genes normally activated by ESRRA. The mutations they identified affected this interaction, acting to suppress the activity of genes normally activated by ESRRA; they suggest that the two proteins must interact as part of a biological pathway that is disrupted in eating disorders.
Next they plan to determine whether or not these genes are affected in sporadic cases of EDs and investigate whether or not oestrogen (estrogen) signalling is involved, as well as finding out more about how the pathway functions.
Comment: The two genes identified are most unlikely to be the only ones involved, but they may help direct the search for others; biological handles are badly needed for these poorly understood conditions for which current psychological treatment approaches show only limited efficacy and new therapeutics are needed. Just as patients with rare and severe forms of obesity have helped to develop better understanding of the pathways involved in the regulation of hunger and energy intake, these unusual (and unfortunate) families may also have helped with respect to eating disorders.