Bipolar disorder with binge eating behavior: A genome-wide association study implicates PRR5-ARHGAP8

Susan L. McElroy, Stacey J. Winham, Alfredo B. Cuellar-Barboza, Colin L. Colby, Ada Man Choi Ho, Hugues Sicotte, Beth R. Larrabee, Scott Crow, Mark A. Frye, Joanna M. Biernacka

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Abstract

Bipolar disorder (BD) is associated with binge eating behavior (BE), and both conditions are heritable. Previously, using data from the Genetic Association Information Network (GAIN) study of BD, we performed genome-wide association (GWA) analyses of BD with BE comorbidity. Here, utilizing data from the Mayo Clinic BD Biobank (969 BD cases, 777 controls), we performed a GWA analysis of a BD subtype defined by BE, and case-only analysis comparing BD subjects with and without BE. We then performed a meta-analysis of the Mayo and GAIN results. The meta-analysis provided genome-wide significant evidence of association between single nucleotide polymorphisms (SNPs) in PRR5-ARHGAP8 and BE in BD cases (rs726170 OR = 1.91, P = 3.05E-08). In the meta-analysis comparing cases with BD with comorbid BE vs. non-BD controls, a genome-wide significant association was observed at SNP rs111940429 in an intergenic region near PPP1R2P5 (p = 1.21E-08). PRR5-ARHGAP8 is a read-through transcript resulting in a fusion protein of PRR5 and ARHGAP8. PRR5 encodes a subunit of mTORC2, a serine/threonine kinase that participates in food intake regulation, while ARHGAP8 encodes a member of the RhoGAP family of proteins that mediate cross-talk between Rho GTPases and other signaling pathways. Without BE information in controls, it is not possible to determine whether the observed association reflects a risk factor for BE in general, risk for BE in individuals with BD, or risk of a subtype of BD with BE. The effect of PRR5-ARHGAP8 on BE risk thus warrants further investigation.

Original languageEnglish (US)
Article number40
JournalTranslational psychiatry
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

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Bulimia
Genome-Wide Association Study
Feeding Behavior
Bipolar Disorder
Risk-Taking
Meta-Analysis
Information Services
Single Nucleotide Polymorphism
Genome
Appetite Regulation
rho GTP-Binding Proteins
Intergenic DNA
Protein-Serine-Threonine Kinases
Comorbidity
Proteins

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

Cite this

McElroy, S. L., Winham, S. J., Cuellar-Barboza, A. B., Colby, C. L., Ho, A. M. C., Sicotte, H., ... Biernacka, J. M. (2018). Bipolar disorder with binge eating behavior: A genome-wide association study implicates PRR5-ARHGAP8. Translational psychiatry, 8(1), [40]. https://doi.org/10.1038/s41398-017-0085-3

Bipolar disorder with binge eating behavior : A genome-wide association study implicates PRR5-ARHGAP8. / McElroy, Susan L.; Winham, Stacey J.; Cuellar-Barboza, Alfredo B.; Colby, Colin L.; Ho, Ada Man Choi; Sicotte, Hugues; Larrabee, Beth R.; Crow, Scott; Frye, Mark A.; Biernacka, Joanna M.

In: Translational psychiatry, Vol. 8, No. 1, 40, 01.12.2018.

Research output: Contribution to journalArticle

McElroy, SL, Winham, SJ, Cuellar-Barboza, AB, Colby, CL, Ho, AMC, Sicotte, H, Larrabee, BR, Crow, S, Frye, MA & Biernacka, JM 2018, 'Bipolar disorder with binge eating behavior: A genome-wide association study implicates PRR5-ARHGAP8', Translational psychiatry, vol. 8, no. 1, 40. https://doi.org/10.1038/s41398-017-0085-3
McElroy, Susan L. ; Winham, Stacey J. ; Cuellar-Barboza, Alfredo B. ; Colby, Colin L. ; Ho, Ada Man Choi ; Sicotte, Hugues ; Larrabee, Beth R. ; Crow, Scott ; Frye, Mark A. ; Biernacka, Joanna M. / Bipolar disorder with binge eating behavior : A genome-wide association study implicates PRR5-ARHGAP8. In: Translational psychiatry. 2018 ; Vol. 8, No. 1.
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abstract = "Bipolar disorder (BD) is associated with binge eating behavior (BE), and both conditions are heritable. Previously, using data from the Genetic Association Information Network (GAIN) study of BD, we performed genome-wide association (GWA) analyses of BD with BE comorbidity. Here, utilizing data from the Mayo Clinic BD Biobank (969 BD cases, 777 controls), we performed a GWA analysis of a BD subtype defined by BE, and case-only analysis comparing BD subjects with and without BE. We then performed a meta-analysis of the Mayo and GAIN results. The meta-analysis provided genome-wide significant evidence of association between single nucleotide polymorphisms (SNPs) in PRR5-ARHGAP8 and BE in BD cases (rs726170 OR = 1.91, P = 3.05E-08). In the meta-analysis comparing cases with BD with comorbid BE vs. non-BD controls, a genome-wide significant association was observed at SNP rs111940429 in an intergenic region near PPP1R2P5 (p = 1.21E-08). PRR5-ARHGAP8 is a read-through transcript resulting in a fusion protein of PRR5 and ARHGAP8. PRR5 encodes a subunit of mTORC2, a serine/threonine kinase that participates in food intake regulation, while ARHGAP8 encodes a member of the RhoGAP family of proteins that mediate cross-talk between Rho GTPases and other signaling pathways. Without BE information in controls, it is not possible to determine whether the observed association reflects a risk factor for BE in general, risk for BE in individuals with BD, or risk of a subtype of BD with BE. The effect of PRR5-ARHGAP8 on BE risk thus warrants further investigation.",
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