Multivariate GWAS identifies 248 loci for internalizing disorder and 591 for major depressive disorder in millions of participants.

This study utilized a multivariate and multi-ancestry genome-wide association approach to examine genetic contributions to generalized anxiety disorder, major depressive disorder, and posttraumatic stress disorder. The analysis included millions of ancestrally diverse participants, with specific sample sizes of 1,358,762 for generalized anxiety disorder, 3,601,629 for major depressive disorder, and 1,617,876 for posttraumatic stress disorder. Genetic variants served as the primary exposure of interest across this large-scale investigation.

The primary results revealed 248 loci associated with a latent internalizing disorder factor. Additionally, 591 loci were associated with major depressive disorder, while 237 loci were associated with posttraumatic stress disorder. For generalized anxiety disorder specifically, 109 loci were identified as associated. Regarding the latent internalizing disorder factor, 38% of the genetic signals were found to be disorder-specific rather than shared across conditions. Furthermore, the study uncovered more than 450 causal variants and identified more than 1,250 genes linked to these variants.

Safety and tolerability data were not reported in this genetic association study, as adverse events are not applicable to genomic exposures. The study design and population characteristics were not fully detailed in the provided input, and specific settings were not reported. Key limitations include the absence of reported effect sizes, confidence intervals, or p-values for the identified associations. Additionally, the study phase and publication type were not reported. These findings describe genetic associations within a specific population and may not be directly translatable to individual patient risk prediction or immediate clinical practice without further validation.