CORRELATION BETWEEN GENE EXPRESSION CHANGE AND HORMONE CHANGE DURING REFEEDING IN ANOREXIA NERVOSA

Background Anorexia Nervosa (AN) is an eating disorder characterized by extreme food restriction, resulting in a body weight that is less then minimally expected. Genetic factors contribute to its etiology with heritability estimates ranging between 48%-74%. The first genome-wide significant locus for AN has been identified, and AN shows moderate and significant genetic correlations with additional psychiatric and somatic phenotypes. Transcriptome expression profiling has also been applied to AN to assess whether gene expression levels change with AN treatment. One study completed whole transcriptome expression profiling and compared expression levels at hospital admission and discharge. Sixty-seven genes were significantly differentially expressed. Similarly, other biological factors change during the treatment process for AN. Norepinephrine and ghrelin levels decrease with weight gain whereas adiponectin, estradiol, and glucose increase. It is unclear how changes in gene expression are associated with changes in other biological factors during weight gain—which we examine here. Methods Change in gene expression from inpatient admission (T1) to discharge (T2) has been previously identified. We explore associations between the top 10 differentially expressed genes and change in appetite (leptin, ghrelin) and reproductive hormones (estradiol), an inflammatory marker (TNF-α), and glucose. Subjects were 6 females receiving treatment for AN. Blood samples were taken at T1 and T2; a PAXgene tube used to collect blood for RNA. 12 samples were sequenced using 1 μg of total RNA as input. Samples were randomized and sequencing libraries prepared using Illumina TruSeq RNA Sample Preparation Kit v2. Libraries were quantitated using fluorometry and samples were pooled at equimolar concentrations prior to sequencing. Two lanes of Illumina HiSeq. 2000 generated a total of 381million 100 bp paired-end reads. Following quality control, we used a standard RNAseq alignment and analysis pipeline. A difference score (T2- T1) was created for the variables to explore the association between gene expression change and change in other biological factors. Results The top 10 previously identified differentially expressed genes included in this study: C16orf11, CYP11A1, DEFA10P, LINC00235, DSP, OLR1, CPA3, FMO3, AKAp12, and GATA2. Two significant correlations (p Discussion Change in CPA3 and GATA2 expression were positively associated with change in leptin. Little is known about the function of these genes. However, CPA3 is expressed in mast cells, which are immune cells contributing to the pathogenesis of obesity, diabetes, and other inflammatory diseases. GATA2 may be involved in dendritic cell, monocyte, B lymphocyte, and natural killer lymphocyte deficiency. In turn, leptin represents a link between nutritional status and immune response. Thus, factors that represent indirect makers of the body's immune and inflammation response appear to move in tandem during the refeeding process in AN. This aligns with work suggesting genetic overlap between AN, autoimmune disease, and markers of metabolic health. The genetic architecture of AN suggests it may be best conceptualized as both a metabolic disease and a psychiatric illness.