title: A genome-wide association study of emotion dysregulation: Evidence for interleukin 2 receptor alpha.
abstract: Emotion dysregulation has been implicated as a risk factor for many psychiatric conditions. Therefore, examining genetic risk associated with emotion dysregulation could help inform cross-disorder risk more generally. A genome-wide association study (GWAS) of emotion dysregulation using single nucleotide polymorphism (SNP) array technology was conducted in a highly traumatized, minority, urban sample (N = 2600, males = 774). Post-hoc analyses examined associations between SNPs identified in the GWAS and current depression, posttraumatic stress disorder (PTSD), and history of suicide attempt. Methylation quantitative trait loci were identified and gene set enrichment analyses were used to broadly determine biological processes involved with these SNPs. Among males, SNP rs6602398, located within the interleukin receptor 2A gene, IL2RA, was significantly associated with emotion dysregulation (p = 1.1 × 10-8). Logistic regression analyses revealed this SNP was significantly associated with depression (Exp(B) = 2.67, p < 0.001) and PTSD (Exp(B) = 2.07, p < 0.01). This SNP was associated with differential DNA methylation (p < 0.05) suggesting it may be functionally active. Finally, through gene set enrichment analyses, ten psychiatric disease pathways (adjusted p < 0.01) and the calcium signaling pathway (adjusted p = 0.008) were significantly associated with emotion dysregulation. We found initial evidence for an association between emotion dysregulation and genetic risk loci that have already been implicated in medical disorders that have high comorbidity with psychiatric disorders. Our results provide further evidence that emotion dysregulation can be understood as a potential psychiatric cross-disorder risk factor, and that sex differences across these phenotypes may be critical. Continued research into genetic and biological risk associated with emotion dysregulation is needed.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, United States. Electronic address: adpower@emory.edu.
authors.forename: Abigail
authors.initials: A
authors.lastname: Powers
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, United States.
authors.forename: Lynn
authors.initials: L
authors.lastname: Almli
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, United States.
authors.forename: Alicia
authors.initials: A
authors.lastname: Smith
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, United States.
authors.forename: Adriana
authors.initials: A
authors.lastname: Lori
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, United States.
authors.forename: Jen
authors.initials: J
authors.lastname: Leveille
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, United States; McLean Hospital, Harvard Medical School, United States.
authors.forename: Kerry J
authors.initials: KJ
authors.lastname: Ressler
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, United States.
authors.forename: Tanja
authors.initials: T
authors.lastname: Jovanovic
authors.affiliation: Atlanta VA Medical Center, United States; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, United States.
authors.forename: Bekh
authors.initials: B
authors.lastname: Bradley
mesh_terms: D000293:Adolescent; D000328:Adult; D000342:Affective Symptoms / Q000235:genetics*; D000368:Aged; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D012307:Risk Factors; D012727:Sex Characteristics; D055815:Young Adult
chemical_list: D053645:Interleukin-2 Receptor alpha Subunit
keywords: Emotion dysregulation; Genetics; Genome-wide association study; Transdiagnostic risk; Traumatized population