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.
Highlights
Bipolar disorder (BD) and binge eating behavior (BE)co-occur more often than expected by chance[1,2,3]
BD cases met DSM-IV criteria for bipolar I disorder or schizoaffective disorder determined by psychiatric interviews based on the Diagnostic Interview for Genetic Studies (DIGS) 2, 3, or 4, which included the question, “has there ever been a time in your life when you went on food binges?”
The meta-analysis of BE in BD cases provided genome-wide significant evidence for association of BE with a group of single nucleotide polymorphisms (SNPs) in the PRR5-ARHGAP8 gene, where the more common allele is associated with reduced risk of BE behavior among BD patients; the C allele at rs726170 is less common in BD patients with BE (Mayo 0.84, Genetic Association Information Network (GAIN) 0.81) as compared to those without BE (Mayo 0.89, GAIN 0.90)
Summary
Bipolar disorder (BD) and binge eating behavior (BE)co-occur more often than expected by chance[1,2,3]. Bipolar disorder (BD) and binge eating behavior (BE). Estimated to occur in 4.5% of the United States general population, BE has been reported to occur in over 25% of individuals with BD1,2. Defined as eating an unusually large amount of food in a discrete time period with a sense of loss of control over the eating, BE is a transdiagnostic feature of eating disorders: it is a defining symptom of bulimia nervosa and binge eating disorder, and may occur in anorexia nervosa. Few studies have evaluated the genetic architecture of the co-occurrence of BD and BE. Genetic studies of specific BD sub-phenotypes may help uncover some of the unknown inheritance of BD. In an earlier study using data from the Genetic Association Information Network (GAIN) study of BD, we conducted a genome-wide association (GWA) analysis of BD subtypes defined by the presence or absence of a history of BE and a case-only
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