Shared Genetic Basis, Biological Function and Causal Relationship Between Sleep Traits and Hypothyroidism: Evidence from a Comprehensive Genetic Analysis.

Yinli Shi, Ming Guo, Yuedan Wang, Guoduan Zeng, Wenting Li, Mianhua Wu, Bo Li
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Abstract

Background: This research attempts to clarify whether there are any genetic similarities between sleep traits and hypothyroidism based on publicly accessible large-scale genomewide association studies.

Methods: The methodology included colocalization analysis, crossphenotype association analysis, and linkage disequilibrium score regression analysis to find common genetic overlap. Through tissue function specificity and functional mapping, we were able to identify the shared genetic level. Genetic instrumental factors were used for causal inference in two-sample univariate and multivariable Mendelian randomization analyses.

Results: A hereditary correlation between hypothyroidism and napping during the day and getting up in the morning (rg=-0.0982, P=0.0007; rg=-0.101, P=0.0001). MAGI3, and HLA-DRB1 BX296568.1 may be potential targets for shared treatments. Colocalization and tissue-specific analysis demonstrated that the common genes and SNPs were identified in the thyroid, lung, brain, and lymphatic tissues. Functional analysis emphasized the importance of these common genes in processes like as protein transport, inflammatory response, and MHC class II protein synthesis. Furthermore, an association has been established between hypothyroidism and sleep duration (IVW, OR 1.5208; 95% CI 1.1142-2.0758, P=0.0082) and getting up in the morning (IVW, OR 1.8375; 95%CI: 1.4502-2.3284, P=4.73E-07). Furthermore, the reverse MR analysis revealed no causal connection between aberrant sleep traits and hypothyroidism. The enduring impact of insomnia on hypothyroidism persists despite controlling for alcohol consumption and smoking habits.

Conclusion: Certain genetic correlations between sleep traits and hypothyroidism have been emphasized. These findings may elucidate the origin of comorbidity and have implications for future clinical trials.

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睡眠特征与甲状腺功能减退症的共同遗传基础、生物学功能和因果关系:来自综合遗传分析的证据。
背景:本研究试图通过公开的大规模全基因组关联研究来阐明睡眠特征和甲状腺功能减退症之间是否存在遗传相似性。方法:采用共定位分析、交叉表型关联分析、连锁不平衡评分回归分析等方法寻找共同遗传重叠。通过组织功能特异性和功能定位,我们能够确定共享的遗传水平。在双样本单变量和多变量孟德尔随机化分析中,遗传工具因子用于因果推理。结果:甲状腺功能减退与白天午睡和早晨起床存在遗传相关性(rg=-0.0982, P=0.0007;rg = -0.101, P = 0.0001)。MAGI3和HLA-DRB1 BX296568.1可能是共享治疗的潜在靶点。共定位和组织特异性分析表明,在甲状腺、肺、脑和淋巴组织中发现了共同的基因和snp。功能分析强调了这些常见基因在蛋白质转运、炎症反应和MHC II类蛋白质合成等过程中的重要性。此外,甲状腺功能减退症与睡眠时间之间存在关联(IVW, OR 1.5208;95% CI 1.1142-2.0758, P=0.0082)和早晨起床(IVW, OR 1.8375;95%ci: 1.4502-2.3284, p = 4.73e-07)。此外,反向核磁共振分析显示,异常睡眠特征和甲状腺功能减退之间没有因果关系。尽管控制了饮酒和吸烟习惯,失眠对甲状腺功能减退的持久影响仍然存在。结论:睡眠特征与甲状腺功能减退之间存在一定的遗传相关性。这些发现可能阐明了合并症的起源,并对未来的临床试验具有指导意义。
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