Exploring the Genetic Correlation Between Pituitary Adenomas and Psychiatric Disorders: Insights From Genome-Wide Association Studies.

BACKGROUND

Pituitary adenomas (PA) exhibit complex comorbidity with various psychiatric disorders, suggesting a potential shared genetic basis.

OBJECTIVE

This study aims to explore the genetic correlation between PA and 8 psychiatric disorders, revealing potential shared pathogenic mechanisms.

METHODS

This study utilized large-scale genome-wide association study (GWAS) summary data to systematically assess the genetic relationships between PA and psychiatric disorders through global genetic correlation analysis, local genetic correlation analysis, summary-data-based Mendelian randomization (SMR), and multitrait analysis of pleiotropic loci (MTAG).

RESULTS

The study found significant genome-wide genetic correlations between PA and schizophrenia, anxiety disorders, bipolar disorder, and depression. Local genetic correlation analysis identified several significant regions, with 1674 (chr11: 64594823-66782661) prominently associated with PA's correlations with bipolar disorder (BD) and major depressive disorder (MDD). MTAG identified 1463 potential pleiotropic loci, whereas SMR analysis revealed 287 pleiotropic genes. Tissue-specific analysis and pathway enrichment analysis indicated that these genes are primarily enriched in synaptic transmission and ion channel activity pathways related to the hypothalamic-pituitary-adrenal (HPA) axis.

CONCLUSION

This study provides important evidence for understanding the genetic association between pituitary adenomas and psychiatric disorders, emphasizing the role of the HPA axis in the shared genetic etiology of both disease types and guiding future intervention strategies.