Genome-wide meta-analysis of panic attacks and disorder identifies genetic risk factors and implicates multiple body systems in panic and other psychiatric disorders

Abstract

Panic attacks are sudden episodes of intense fear with physical and psychological symptoms, affecting approximately 28% of the population. Panic disorder (3-7% prevalence) involves recurrent attacks with persistent anticipatory worry, functional impairment, and avoidance. We conducted genome-wide association meta-analyses of a broad panic phenotype (panic attacks or panic disorder; 90,840 cases, 201,638 controls), panic disorder (41,721 cases, 201,638 controls), and isolated panic attacks (49,119 cases, 192,885 controls), identifying the first genome-wide significant variants for each trait (25 broad, 15 disorder, 5 attack). Gene-set analysis of single-cell RNA sequencing data for the broad phenotype implicated eye, heart, and lung neurons, pointing to sensory processing and interoceptive awareness. These peripheral neuronal associations generalised across psychiatric disorders. These findings offer novel insights into the biological mechanisms underlying panic and the overlooked role of afferent neurons across psychiatric disorders.