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Abstract
Anorexia nervosa is a complex eating disorder with genetic, metabolic, and psychosocial underpinnings. Using genome-wide methods, recent studies have associated many genes with the disorder. We characterized these genes by projecting them into reference transcriptomic atlases of the prenatal and adult human brain to determine where these genes are expressed in fine detail. We found that genes from an induced stem cell study of anorexia nervosa cases are expressed at higher levels in the lateral parabrachial nucleus. Although weaker, expression enrichment of the adult lateral parabrachial is also found with genes from independent genetic studies. Candidate causal genes from the largest genetic study of anorexia nervosa to date were enriched for expression in the arcuate nucleus of the hypothalamus. We also found an enrichment of anorexia nervosa associated genes in the adult and fetal raphe and ventral tegmental areas. Motivated by enrichment of these feeding circuits, we tested if these genes respond to fasting in mice hypothalami, which highlighted the differential expression of Rps26 and Dalrd3. This work improves our understanding of the neurobiology of anorexia nervosa by suggesting disturbances in subcortical appetitive circuits.
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1 Centre for Addiction and Mental Health, Campbell Family Mental Health Research Institute, Toronto, Canada (GRID:grid.155956.b) (ISNI:0000 0000 8793 5925); Centre for Addiction and Mental Health, Krembil Centre for Neuroinformatics, Toronto, Canada (GRID:grid.155956.b) (ISNI:0000 0000 8793 5925)
2 University of California San Diego, Department of Pediatrics, School of Medicine, La Jolla, USA (GRID:grid.266100.3) (ISNI:0000 0001 2107 4242)
3 Centre for Addiction and Mental Health, Campbell Family Mental Health Research Institute, Toronto, Canada (GRID:grid.155956.b) (ISNI:0000 0000 8793 5925); University of Toronto, Institute for Medical Science, Toronto, Canada (GRID:grid.17063.33) (ISNI:0000 0001 2157 2938); Centre for Addiction and Mental Health, Slaight Family Centre for Youth in Transition, Toronto, Canada (GRID:grid.155956.b) (ISNI:0000 0000 8793 5925); University of Toronto, Department of Psychiatry, Toronto, Canada (GRID:grid.17063.33) (ISNI:0000 0001 2157 2938)
4 Centre for Addiction and Mental Health, Campbell Family Mental Health Research Institute, Toronto, Canada (GRID:grid.155956.b) (ISNI:0000 0000 8793 5925); University of Toronto, Institute for Medical Science, Toronto, Canada (GRID:grid.17063.33) (ISNI:0000 0001 2157 2938); University of Toronto, Department of Psychiatry, Toronto, Canada (GRID:grid.17063.33) (ISNI:0000 0001 2157 2938)
5 University of California San Diego, Department of Pediatrics/Cellular and Molecular Medicine, La Jolla, USA (GRID:grid.266100.3) (ISNI:0000 0001 2107 4242); University of California San Diego, Kavli Institute for Brain and Mind, La Jolla, USA (GRID:grid.266100.3) (ISNI:0000 0001 2107 4242); Rady Children’s Hospital, San Diego, USA (GRID:grid.286440.c) (ISNI:0000 0004 0383 2910)
6 University of California San Diego, Department of Pediatrics and Psychiatry, School of Medicine, La Jolla, USA (GRID:grid.266100.3) (ISNI:0000 0001 2107 4242)
7 Centre for Addiction and Mental Health, Campbell Family Mental Health Research Institute, Toronto, Canada (GRID:grid.155956.b) (ISNI:0000 0000 8793 5925); Centre for Addiction and Mental Health, Krembil Centre for Neuroinformatics, Toronto, Canada (GRID:grid.155956.b) (ISNI:0000 0000 8793 5925); University of Toronto, Institute for Medical Science, Toronto, Canada (GRID:grid.17063.33) (ISNI:0000 0001 2157 2938); University of Toronto, Department of Psychiatry, Toronto, Canada (GRID:grid.17063.33) (ISNI:0000 0001 2157 2938)