Isolating transdiagnostic effects reveals specific genetic profiles in psychiatric disorders.

Abstract Evidence indicates a great degree of genetic overlap between psychiatric diagnoses. Accounting for these transdiagnostic effects can sharpen research on disorder-specific genetic architecture. Here we isolate genetic effects that are shared across 11 major psychiatric disorders (p factor) to gain further insight into genetic specificity and comorbidity over and above that contributed by the p factor, unique to each psychiatric disorder. After adjusting for transdiagnostic genetic effects, we identified novel SNP associations and some changes in enrichment patterns. We examined genetic correlations among adjusted psychiatric traits as well as relationships with other biobehavioural traits. The landscape of genetic associations between pairs of psychiatric disorders changed substantially, and their genetic correlations with biobehavioural traits showed greater specificity. Isolating transdiagnostic genetic effects across major psychiatric disorders provides a nuanced understanding of disorder-specific genetic architecture and may help guide diagnostic nomenclature and treatment research.