Novel and ultra-rare damaging variants in neuropeptide signaling are associated with disordered eating behaviors.
OBJECTIVE:Eating disorders develop through a combination of genetic vulnerability and environmental stress, however the genetic basis of this risk is unknown. METHODS:To understand the genetic basis of this risk, we performed whole exome sequencing on 93 unrelated individuals with eating disorders (...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5573281?pdf=render |
| _version_ | 1828483739176402944 |
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| author | Michael Lutter Ethan Bahl Claire Hannah Dabney Hofammann Summer Acevedo Huxing Cui Carrie J McAdams Jacob J Michaelson |
| author_facet | Michael Lutter Ethan Bahl Claire Hannah Dabney Hofammann Summer Acevedo Huxing Cui Carrie J McAdams Jacob J Michaelson |
| author_sort | Michael Lutter |
| collection | DOAJ |
| description | OBJECTIVE:Eating disorders develop through a combination of genetic vulnerability and environmental stress, however the genetic basis of this risk is unknown. METHODS:To understand the genetic basis of this risk, we performed whole exome sequencing on 93 unrelated individuals with eating disorders (38 restricted-eating and 55 binge-eating) to identify novel damaging variants. Candidate genes with an excessive burden of predicted damaging variants were then prioritized based upon an unbiased, data-driven bioinformatic analysis. One top candidate pathway was empirically tested for therapeutic potential in a mouse model of binge-like eating. RESULTS:An excessive burden of novel damaging variants was identified in 186 genes in the restricted-eating group and 245 genes in the binge-eating group. This list is significantly enriched (OR = 4.6, p<0.0001) for genes involved in neuropeptide/neurotrophic pathways implicated in appetite regulation, including neurotensin-, glucagon-like peptide 1- and BDNF-signaling. Administration of the glucagon-like peptide 1 receptor agonist exendin-4 significantly reduced food intake in a mouse model of 'binge-like' eating. CONCLUSIONS:These findings implicate ultra-rare and novel damaging variants in neuropeptide/neurotropic factor signaling pathways in the development of eating disorder behaviors and identify glucagon-like peptide 1-receptor agonists as a potential treatment for binge eating. |
| first_indexed | 2024-12-11T08:43:07Z |
| format | Article |
| id | doaj.art-4b06b77a94bf4d7e89fd98d4b2ca737f |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T08:43:07Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-4b06b77a94bf4d7e89fd98d4b2ca737f2022-12-22T01:14:13ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01128e018155610.1371/journal.pone.0181556Novel and ultra-rare damaging variants in neuropeptide signaling are associated with disordered eating behaviors.Michael LutterEthan BahlClaire HannahDabney HofammannSummer AcevedoHuxing CuiCarrie J McAdamsJacob J MichaelsonOBJECTIVE:Eating disorders develop through a combination of genetic vulnerability and environmental stress, however the genetic basis of this risk is unknown. METHODS:To understand the genetic basis of this risk, we performed whole exome sequencing on 93 unrelated individuals with eating disorders (38 restricted-eating and 55 binge-eating) to identify novel damaging variants. Candidate genes with an excessive burden of predicted damaging variants were then prioritized based upon an unbiased, data-driven bioinformatic analysis. One top candidate pathway was empirically tested for therapeutic potential in a mouse model of binge-like eating. RESULTS:An excessive burden of novel damaging variants was identified in 186 genes in the restricted-eating group and 245 genes in the binge-eating group. This list is significantly enriched (OR = 4.6, p<0.0001) for genes involved in neuropeptide/neurotrophic pathways implicated in appetite regulation, including neurotensin-, glucagon-like peptide 1- and BDNF-signaling. Administration of the glucagon-like peptide 1 receptor agonist exendin-4 significantly reduced food intake in a mouse model of 'binge-like' eating. CONCLUSIONS:These findings implicate ultra-rare and novel damaging variants in neuropeptide/neurotropic factor signaling pathways in the development of eating disorder behaviors and identify glucagon-like peptide 1-receptor agonists as a potential treatment for binge eating.http://europepmc.org/articles/PMC5573281?pdf=render |
| spellingShingle | Michael Lutter Ethan Bahl Claire Hannah Dabney Hofammann Summer Acevedo Huxing Cui Carrie J McAdams Jacob J Michaelson Novel and ultra-rare damaging variants in neuropeptide signaling are associated with disordered eating behaviors. PLoS ONE |
| title | Novel and ultra-rare damaging variants in neuropeptide signaling are associated with disordered eating behaviors. |
| title_full | Novel and ultra-rare damaging variants in neuropeptide signaling are associated with disordered eating behaviors. |
| title_fullStr | Novel and ultra-rare damaging variants in neuropeptide signaling are associated with disordered eating behaviors. |
| title_full_unstemmed | Novel and ultra-rare damaging variants in neuropeptide signaling are associated with disordered eating behaviors. |
| title_short | Novel and ultra-rare damaging variants in neuropeptide signaling are associated with disordered eating behaviors. |
| title_sort | novel and ultra rare damaging variants in neuropeptide signaling are associated with disordered eating behaviors |
| url | http://europepmc.org/articles/PMC5573281?pdf=render |
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