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

Area of Science:

• Genetics
• Psychiatry
• Neuroscience

Background:

• Bipolar disorder (BD) frequently co-occurs with binge eating (BE) behavior.
• Both BD and BE are known to have a significant heritable component.
• Previous genome-wide association (GWA) studies have explored the genetic overlap between BD and BE.

Purpose of the Study:

• To identify genetic loci associated with binge eating (BE) in individuals with bipolar disorder (BD).
• To conduct a meta-analysis of existing and new GWA data to increase statistical power.
• To investigate specific genes and their potential roles in the comorbidity of BD and BE.

Main Methods:

• Genome-wide association (GWA) analysis was performed on data from the Mayo Clinic Bipolar Disorder Biobank (969 cases, 777 controls).
• Case-only analysis compared BD subjects with and without comorbid BE.
• Meta-analysis combined results from the Mayo Clinic study and the prior Genetic Association Information Network (GAIN) study.

Main Results:

• Meta-analysis identified genome-wide significant association between SNPs in PRR5-ARHGAP8 and BE in BD cases (rs726170, P=3.05E-08).
• A separate meta-analysis revealed genome-wide significant association at SNP rs111940429 near PPP1R2P5 when comparing BD cases with BE to non-BD controls (P=1.21E-08).
• PRR5-ARHGAP8 encodes a fusion protein involving mTORC2 (food intake regulation) and RhoGAP (signaling pathways).

Conclusions:

• The study provides genome-wide significant evidence for genetic loci associated with binge eating in bipolar disorder.
• The gene PRR5-ARHGAP8, implicated in food intake regulation and signaling pathways, is a key finding.
• Further research is needed to clarify whether the identified genetic associations relate to general BE risk, BE risk specifically in BD, or a distinct BD subtype characterized by BE.