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Cited by 71Eating Disorders and BehaviorsRegulation of Appetite and ObesityChild Nutrition and Feeding Issues

Cytoplasmic FMR1-Interacting Protein 2 Is a Major Genetic Factor Underlying Binge Eating

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Kirkpatrick, Stacey L., Goldberg, Lisa R., Yazdani, Neema, Babbs, R. Keith, Wu, Jiayi, Reed, Eric R., Jenkins, David F., Bolgioni, Amanda F. +8 more·2017·Biological Psychiatry
DOI 10.1016/j.biopsych.2016.10.021PMC PMC5386810
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Abstract

Background Eating disorders are lethal and heritable; however, the underlying genetic factors are unknown. Binge eating is a highly heritable trait associated with eating disorders that is comorbid with mood and substance use disorders. Therefore, understanding its genetic basis will inform therapeutic development that could improve several comorbid neuropsychiatric conditions. Methods We assessed binge eating in closely related C57BL/6 mouse substrains and in an F 2 cross to identify quantitative trait loci associated with binge eating. We used gene targeting to validate candidate genetic factors. Finally, we used transcriptome analysis of the striatum via messenger RNA sequencing to identify the premorbid transcriptome and the binge-induced transcriptome to inform molecular mechanisms mediating binge eating susceptibility and establishment. Results C57BL/6NJ but not C57BL/6J mice showed rapid and robust escalation in palatable food consumption. We mapped a single genome-wide significant quantitative trait locus on chromosome 11 (logarithm of the odds = 7.4) to a missense mutation in cytoplasmic FMR1-interacting protein 2 (Cyfip2). We validated Cyfip2 as a major genetic factor underlying binge eating in heterozygous knockout mice on a C57BL/6N background that showed reduced binge eating toward a wild-type C57BL/6J-like level. Transcriptome analysis of premorbid genetic risk identified the enrichment terms morphine addiction and retrograde endocannabinoid signaling, whereas binge eating resulted in the downregulation of a gene set enriched for decreased myelination, oligodendrocyte differentiation, and expression. Conclusions We identified Cyfip2 as a major significant genetic factor underlying binge eating and provide a behavioral paradigm for future genome-wide association studies in populations with increased genetic complexity.

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  • Because CYFIP1 is deleted or imprinted in patients with type I Prader-Willi syndrome, an NDD defined by extreme hyperphagia and a hyperresponsive reward system to food-associated cues, the shared biological functions of CYFIP1 and 2 might be associated with maladaptive feeding in humans.

    “Because CYFIP1 is deleted or imprinted in patients with type I Prader–Willi syndrome, an NDD defined by extreme hyperphagia and a hyperresponsive reward system to food-associated cues, the shared biological functions of CYFIP1 and 2 might be associated with maladaptive feeding in humans177,178.”

    From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [177]

  • Cyfip2 heterozygous knockout mice on a C57BL/6N background presented reduced binge eating comparable to that of wild-type C57BL/6J-like mice.

    “Cyfip2 heterozygous KO mice on a C57BL/6N background presented reduced binge eating comparable to that of wild-type C57BL/6J-like mice.”

    From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [177]

  • C57BL/6N mice, but not C57BL/6J mice, showed rapid and robust escalation in palatable food consumption.

    “C57BL/6N mice, but not C57BL/6J mice, showed rapid and robust escalation in palatable food consumption.”

    From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [177]

  • CYFIP2 was also identified as a significant genetic factor underlying binge eating by analyzing closely related C57BL/6 mouse substrains.

    “CYFIP2 was also identified as a significant genetic factor underlying binge eating by analyzing closely related C57BL/6 mouse substrains177.”

    From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [177]

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Authors
Kirkpatrick, S. L., Goldberg, L. R., Yazdani, N., Babbs, R. K., Wu, J., Reed, E. R., Jenkins, D. F., Bolgioni, A. F., Landaverde, K. I., Luttik, K. P., Mitchell, K. S., Kumar, V., Johnson, W. E., Mulligan, M. K., Cottone, P., & Bryant, C. D.
Affiliations
  • Boston University (US)
  • Jackson Laboratory (US)
  • University of Tennessee Health Science Center (US)
Corresponding author
Bryant, Camron D.
ORCID
Venue
Biological Psychiatry
Publisher
Elsevier BV
Published
2017-05
Volume
81
Issue
9
Pages
757-769
ISSN
0006-3223 (ISSN-L)
DOI
10.1016/j.biopsych.2016.10.021
PMC
PMC5386810
OpenAlex
W2533849857
Cited by
71
References
7
Citations by year
2026: 1 · 2025: 10 · 2024: 1 · 2023: 6 · 2022: 13 · 2021: 8 · 2020: 7 · 2019: 14 · 2018: 5 · 2017: 6
FWCI
9.76
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Biological Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
Funders
  • National Institute on Drug Abuse (U01DA041668, F31DA040324, R01DA030425, R03DA038287, R00DA029635, R21DA038738)
  • National Institute of General Medical Sciences (T32GM008541)
Topics
  • Social Sciences › Psychology › Clinical Psychology › Eating Disorders and Behaviors
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Health Sciences › Medicine › Psychiatry and Mental health › Child Nutrition and Feeding Issues
Keywords
binge eating, CYFIP2, quantitative trait loci, eating disorders, genetic susceptibility, palatable food consumption, morphine addiction, retrograde endocannabinoid signaling, myelination, oligodendrocyte differentiation, knockout mice
MeSH terms
Animals, Bulimia, Compulsive Behavior, Corpus Striatum, Female, Male, Mice, Inbred C57BL, Nerve Tissue Proteins, Mice, Knockout, Mutation, Missense, Quantitative Trait Loci, Adaptor Proteins, Signal Transducing, Binge-Eating Disorder, Transcriptome

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