Unraveling the Genetic Link Between Endocrine Hormones and Psychiatric Disorders: An Atlas of Genetic Correlations.

Background/objectives: Endocrine hormones play critical roles in regulating physiological processes, and previous studies have reported their associations with psychiatric disorders. Levels of endocrine hormones and the risk of developing psychiatric disorders are influenced by both genetic and non-genetic factors. However, the shared genetic basis underlying these associations remains largely unexplored. This study aims to dually evaluate the genetic correlations among endocrine hormones, including thyroid and sex hormones, as well as between endocrine hormone metrics and psychiatric disorders to identify potential shared genetic architectures.

Methods: We obtained genome-wide association study summary statistics for six thyroid hormone metrics, three sex hormone metrics, and ten psychiatric disorders from predominantly European-ancestry populations. Genetic correlations were computed using linkage disequilibrium score regression after harmonizing variant data to ensure consistency across studies.

Results: Significant genetic correlations were observed among thyroid and sex hormone metrics, indicating a strong shared genetic basis. Sex hormones exhibited multiple genetic correlations with psychiatric disorders, including negative correlations between sex hormone-binding globulin and attention-deficit hyperactivity disorder (ADHD) (p = 3.95 × 10^-12) and major depressive disorder (p = 4.67 × 10^-5), and positive genetic correlations with anorexia nervosa (p = 2.86 × 10^-12) and schizophrenia (p = 2.00 × 10^-4). Testosterone and estradiol had negative genetic correlations with ADHD and major depressive disorder, while testosterone had positive genetic correlations with anorexia nervosa and schizophrenia. Although thyroid hormone metrics did not exhibit Bonferroni-significant genetic correlations, nominal associations were observed, such as a negative genetic correlation between thyroid-stimulating hormone and major depressive disorder (p = 2.33 × 10^-2).

Conclusions: These findings suggest a shared genetic basis between endocrine hormones and psychiatric disorders, particularly for sex hormones. Future studies leveraging larger, more diverse populations are warranted to validate and extend the genetic correlations observed in this study.