High-throughput DNA methylation analysis in anorexia nervosa confirms TNXB hypermethylation

Abstract

We confirm genes like TNXB previously described to comprise differentially methylated sites, and highlight further sites that might be specifically involved in AN starvation processes.

A longitudinal, epigenome-wide study of DNA methylation in anorexia nervosa: results in actively ill, partially weight-restored, long-term remitted and non-eating-disordered women

“…48 In addition, similar to 2 previous studies in anorexia ner vosa, 26,27 we found that TNXB methylation was associated with the presence of anorexia nervosa; the 2 previous studies reported that methylation at this gene was altered in people with anorexia nervosa. 26,27 TNXB has been involved in connectivetissue disorders. Furthermore, the observed decreases in NR1H3 methylation posttreatment was in line with the results of 2 studies showing hyper methylation of this gene in active anorexia nervosa.…”

“…In other words, like the genomewide association study described earlier, 6 our study indicated altered psychiatric, physiologic and immune functions. A subsequent independent study using the same technology compared DNA methylation in 47 women with anorexia nervosa to 100 populationbased controls 27 and identified 81 differentially methylated sites. Both studies isolated the NR1H3 gene (involved in lipid homeostasis and inflammation) and the TNXB gene (associ ated with connectivetissue disorders).…”

“…Furthermore, the observed decreases in NR1H3 methylation posttreatment was in line with the results of 2 studies showing hyper methylation of this gene in active anorexia nervosa. 26,27 Limitations Given the tissue specificity of DNA methylation, 49,50 brain tissue is the optimal medium for epigenetic studies on men tal health entities. However, in the absence of postmortem brain banks for anorexia nervosa, studies such as ours must rely on biomaterials from peripheral tissues.…”

Behavioral Alterations in Mice Carrying Homozygous HDAC4A778T Missense Mutation Associated With Eating Disorder

“…While the family in which ESRRA R188Q mutation was found has a high rate of AN and comorbidity of obsessive-compulsive disorder (OCD), another family in which HDAC4 A786T mutation was found has higher rates of BN but significantly lower rates of comorbid OCD. Multiple independent studies have shown that many CpG sites located in genomic region around 5 upstream of HDAC4 gene are differentially methylated in the peripheral tissues of patients with AN (Booij et al, 2015;Kesselmeier et al, 2018;Subramanian et al, 2018;Sild and Booij, 2019;Steiger et al, 2019), further supporting the role of HDAC4 in the pathophysiology of EDs. In the followup mouse studies, we found that Esrra knockout mice display behavioral deficits relevant to EDs, including reduced food intake, decreased motivation to work for high-fat diet (HFD), and social subordination (Cui et al, 2015).…”

An Evolutionary Genetic Perspective of Eating Disorders

“…Further confirmation of these initial findings is needed at this stage. For instance, the hypermethylation of TNXB has been recently confirmed by high-throughput DNA methylation analysis in AN [106]. Developmental experiences and early adversity can also impact methylation levels of neuropsychiatric genes and, in turn, create variations in phenotypes related to stress reactivity and mood regulation [107].…”