Shared genetic etiology between specific phobia and other psychiatric disorders

Specific phobia is a core anxiety disorder with a moderate genetic component, but its genetic background remains poorly understood. In the current study, the genetic correlations between specific phobia and other psychiatric disorders, including anxiety disorders, as well as intermediate phenotypes, were investigated. Large-scale genome-wide association study (GWAS) summary statistics for specific phobia, indicated by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes during primary care visits or hospital admissions (n = 502,481); 12 psychiatric disorders, including panic disorder and anxiety disorders, from the UK Biobank (UKBB), which primarily consists of generalized anxiety disorder; and 23 intermediate phenotypes were utilized. Linkage disequilibrium score regression (LDSC) analyses were performed to estimate genetic correlations. We visualized the GWAS summary statistics for specific phobia, and no genome-wide significant loci were identified. We also performed a MAGMA tissue-enrichment analysis, and no significant tissue-specific gene expression enrichment was detected, although the brain cerebellum was the most nominally associated tissue (p = 0.059). We found that specific phobia exhibited a strong genetic correlation with panic disorder (r_g = 0.78), followed by adjustment disorder (r_g = 0.69), major depressive disorder (r_g = 0.61), posttraumatic stress disorder (r_g = 0.59), and anxiety disorders from the UKBB (r_g = 0.38). Among the intermediate phenotypes, specific phobia had moderate genetic correlations with neuroticism (r_g = 0.49), a negative genetic correlation with age at first childbirth (r_g = -0.28), a negative genetic correlation with age at first experience of sexual intercourse (r_g = -0.27), and a negative genetic correlation with cognitive performance (r_g = -0.24). No other significant genetic correlations were observed (all p > 0.05). These findings provide insight into the genetic etiology of specific phobia and its relationship with other psychiatric disorders. However, these data are based on clinically identified cases, potentially reflecting more severe or treatment-seeking individuals.