Altered DNA methylation associated with nervosa anorexia in males

Abstract

Purpose: Anorexia nervosa (AN) is a serious psychiatric disorder characterized by abnormal eating behaviors, resulting in weight loss and increased mortality. Although more common in females, an estimated 5 to 10% of affected patients are males. Up to now, the exact cause of male AN is unknown. As with many psychiatric diseases, it's probably a combination of genetic, biological, psychological and environmental factors. Here, we used whole-genome bisulfite sequencing to determine the methylome of male individuals with AN. Methods: We analyzed by bisulfite sequencing 3,340,894 biologically relevant CpG sites (Illumina TruSeqMethyl Capture EPIC kit) of 6 male patients affected with AN restrictive type. To reduce the environment effect, 4 related unaffected individuals were selected as controls. Results: Comparisons between male patients affected with AN restrictive type and unaffected controls showed 153 differentially methylated regions and 1812 differentially methylated CpGs that corresponded to genes relevant to metabolic and nutritional status, psychiatric status and immune function. Moreover, the String network analysis software identified a subnetwork, related to MAPK signaling pathway, PI3K-Akt signaling pathway and neurotrophin signaling pathway. Conclusions: Our findings replicate several results concerning several target genes such as PRKAG2, RPTOR, and ICAM5 previously identified in female AN, and identified novel signaling pathways involving PI3K-Akt and neurotrophin signaling pathway disturbed in AN.