Department of Radiology, Second Xiangya Hospital, Central South University, 139#, Central Renmin Road, Changsha, Hunan Province 410011, People's Republic of China.
Fujian University of Traditional Chinese Medicine, 1#, Qiuyang Road, Fuzhou, Fujian Province 350122, People's Republic of China.
J Affect Disord. 2025 Jan 15;369:312-320. doi: 10.1016/j.jad.2024.08.202. Epub 2024 Sep 29.
Associations between thyroid diseases and psychiatric disorders have been mainly described before. However, the genetic mechanism behind hypothyroidism and psychiatric disorders remains unexplained.
We examined the genetic architecture of hypothyroidism and 8 psychiatric disorders. Firstly, the global and local genetic relationship between the paired traits was explored. Secondly, cross-trait analysis was performed to investigate the genomic loci and genes between psychiatric disorders and hypothyroidism. Thirdly, the significant expression of these genes and the causal relationships were investigated. Lastly, enrichment analysis was conducted on these genes to explore their biological mechanisms.
We observed significant positive genetic correlations between psychiatric disorders and hypothyroidism. The cross-trait meta-analysis identified 62 shared genetic loci between hypothyroidism and psychiatric disorders. The colocalization analysis additionally revealed 15 potential pleiotropic loci with a posterior probabilities.H4 (PP·H4) value >0.7. We also found 2308 genes shared between both traits, which were highly enriched in biological pathways such as immune cell differentiation and autoimmune diseases, as well as in tissue structures like the frontal cortex and cerebral cortex. Especially, many pleiotropic genes were significantly expressed for multiple pairwise traits, such as BCL11B, RERE, and SUOX. Lastly, the Latent causal variable model (LCV) analysis did not find any causal components in the genetic structure between them.
The limitations of this study include that the conclusions were drawn from a European population.
These findings not only deepens our understanding of their biological mechanisms but also has significant implications for the intervention and treatment of these diseases.
甲状腺疾病与精神障碍之间的关联主要在之前已有描述。然而，甲状腺功能减退症与精神障碍之间的遗传机制仍未得到解释。
我们检查了甲状腺功能减退症和 8 种精神障碍的遗传结构。首先，探索了配对特征之间的全局和局部遗传关系。其次，进行了跨特征分析，以研究精神障碍与甲状腺功能减退症之间的基因组位点和基因。第三，调查了这些基因的显著表达及其因果关系。最后，对这些基因进行了富集分析，以探索它们的生物学机制。
我们观察到精神障碍和甲状腺功能减退症之间存在显著的正遗传相关性。跨特征荟萃分析确定了甲状腺功能减退症和精神障碍之间 62 个共享遗传位点。共定位分析还揭示了 15 个潜在的多效性位点，其后验概率.H4（PP·H4）值>0.7。我们还发现了 2308 个在两个特征之间共享的基因，它们在免疫细胞分化和自身免疫性疾病等生物学途径以及额皮质和大脑皮质等组织结构中高度富集。特别是，许多多效性基因在多个成对特征中表达显著，例如 BCL11B、RERE 和 SUOX。最后，潜在因果变量模型（LCV）分析未发现它们之间遗传结构中的任何因果成分。
本研究的局限性在于结论是从欧洲人群中得出的。
这些发现不仅加深了我们对它们的生物学机制的理解，而且对这些疾病的干预和治疗具有重要意义。
