Linda Booij1,2,3, Kevin F Casey2, Juliana M Antunes4, Moshe Szyf5, Ridha Joober3,6, Mimi Israël3,4,6, Howard Steiger3,4,6. 1. Department of Psychology, Queen's University, Kingston, ON, Canada, K7L 3N6. 2. Sainte-Justine Hospital Research Centre, University of Montreal, 3175, Chemin Côte Ste-Catherine, Montreal, QC, Canada, H3T 1C5. 3. Department of Psychiatry, McGill University, Montreal, QC, Canada, H3A1 A1. 4. Eating Disorders Program, Douglas University Institute, 6875 LaSalle Boulevard, Montreal, Quebec, Canada, H4H 1R3. 5. Department of Pharmacology, McGill University, 1309-3655 Sir William Osler Promenade, Montreal, QC, Canada, H3G 1Y6. 6. Research Centre, Douglas University Institute, 6875 LaSalle Boulevard, Montreal, Quebec, Canada, H4H 1R3.
Abstract
OBJECTIVE: Evidence associates anorexia nervosa (AN) with epigenetic alterations that could contribute to illness risk or entrenchment. We investigated the extent to which AN is associated with a distinct methylation profile compared to that seen in normal-eater women. METHOD: Genome-wide methylation profiles, obtained using DNA from whole blood, were determined in 29 women currently ill with AN (10 with AN-restrictive type, 19 with AN-binge/purge type) and 15 normal-weight, normal-eater control women, using 450 K Illumina bead arrays. RESULTS: Regardless of type, AN patients showed higher and less-variable global methylation patterns than controls. False Discovery Rate corrected comparisons identified 14 probes that were hypermethylated in women with AN relative to levels obtained in normal-eater controls, representing genes thought to be associated with histone acetylation, RNA modification, cholesterol storage and lipid transport, and dopamine and glutamate signaling. Age of onset was significantly associated with differential methylation in gene pathways involved in development of the brain and spinal cord, while chronicity of illness was significantly linked to differential methylation in pathways involved with synaptogenesis, neurocognitive deficits, anxiety, altered social functioning, and bowel, kidney, liver and immune function. DISCUSSION: Although pre-existing differences cannot be ruled out, our findings are consistent with the idea of secondary alterations in methylation at genomic regions pertaining to social-emotional impairments and physical sequelae that are commonly seen in AN patients. Further investigation is needed to establish the clinical relevance of the affected genes in AN, and, importantly, reversibility of effects observed with nutritional rehabilitation and treatment.
OBJECTIVE: Evidence associates anorexia nervosa (AN) with epigenetic alterations that could contribute to illness risk or entrenchment. We investigated the extent to which AN is associated with a distinct methylation profile compared to that seen in normal-eater women. METHOD: Genome-wide methylation profiles, obtained using DNA from whole blood, were determined in 29 women currently ill with AN (10 with AN-restrictive type, 19 with AN-binge/purge type) and 15 normal-weight, normal-eater control women, using 450 K Illumina bead arrays. RESULTS: Regardless of type, AN patients showed higher and less-variable global methylation patterns than controls. False Discovery Rate corrected comparisons identified 14 probes that were hypermethylated in women with AN relative to levels obtained in normal-eater controls, representing genes thought to be associated with histone acetylation, RNA modification, cholesterol storage and lipid transport, and dopamine and glutamate signaling. Age of onset was significantly associated with differential methylation in gene pathways involved in development of the brain and spinal cord, while chronicity of illness was significantly linked to differential methylation in pathways involved with synaptogenesis, neurocognitive deficits, anxiety, altered social functioning, and bowel, kidney, liver and immune function. DISCUSSION: Although pre-existing differences cannot be ruled out, our findings are consistent with the idea of secondary alterations in methylation at genomic regions pertaining to social-emotional impairments and physical sequelae that are commonly seen in AN patients. Further investigation is needed to establish the clinical relevance of the affected genes in AN, and, importantly, reversibility of effects observed with nutritional rehabilitation and treatment.
Authors: Hunna J Watson; Alish B Palmos; Avina Hunjan; Jessica H Baker; Zeynep Yilmaz; Helena L Davies Journal: Psychol Med Date: 2021-02-15 Impact factor: 10.592