PDF(Pubmed)
Abstract：
UNASSIGNED: The causative relationship between chronic rhinosinusitis (CRS) and depression remains unclear. Herein we employed Mendelian randomization (MR) coupled with single-cell analysis to investigate the causality between CRS and depression.
UNASSIGNED: Data pertaining to CRS and depression were mined from the genome-wide association study database, and a single-cell dataset was sourced from the literature. To explore causality, we conducted bidirectional MR analysis using MR-Egger, weighted median, inverse variance weighted (IVW), simple mode, and weighted mode, with IVW representing the most important method. Further, sensitivity analysis was performed to evaluate the robustness of MR analysis results. Candidate genes were analyzed via single-cell combined MR analysis.
UNASSIGNED: Forward MR analysis indicated depression as a risk factor for CRS when depression was the exposure factor and CRS was the outcome (OR = 1.425, P < 0.001). Reverse MR analysis revealed the same positive relationship between CRS and depression when CRS was the exposure factor and depression was the outcome (OR = 1.012, P = 0.038). Sensitivity analysis validated the robustness of bidirectional MR analysis results. Ten cell types (endothelial, ciliated, basal, myeloid, mast, apical, plasma, glandular, fibroblast, and T cells) were identified in the single-cell dataset. The network of receptor-ligand pairs showed that in normal samples, cell-cell interactions were present among various cell types, such as epithelial, mast, myeloid, and endothelial cells. In contrast, CRS samples featured only one specific receptor-ligand pair, confined to myeloid cells. TCF4 and MEF2C emerged as potentially crucial for CRS-associated depression development.
UNASSIGNED: Our findings suggest a bidirectional causal relationship between CRS and depression, offering a new perspective on the association between CRS and depression.
UNASSIGNED: Data pertaining to CRS and depression were mined from the genome-wide association study database, and a single-cell dataset was sourced from the literature. To explore causality, we conducted bidirectional MR analysis using MR-Egger, weighted median, inverse variance weighted (IVW), simple mode, and weighted mode, with IVW representing the most important method. Further, sensitivity analysis was performed to evaluate the robustness of MR analysis results. Candidate genes were analyzed via single-cell combined MR analysis.
UNASSIGNED: Forward MR analysis indicated depression as a risk factor for CRS when depression was the exposure factor and CRS was the outcome (OR = 1.425, P < 0.001). Reverse MR analysis revealed the same positive relationship between CRS and depression when CRS was the exposure factor and depression was the outcome (OR = 1.012, P = 0.038). Sensitivity analysis validated the robustness of bidirectional MR analysis results. Ten cell types (endothelial, ciliated, basal, myeloid, mast, apical, plasma, glandular, fibroblast, and T cells) were identified in the single-cell dataset. The network of receptor-ligand pairs showed that in normal samples, cell-cell interactions were present among various cell types, such as epithelial, mast, myeloid, and endothelial cells. In contrast, CRS samples featured only one specific receptor-ligand pair, confined to myeloid cells. TCF4 and MEF2C emerged as potentially crucial for CRS-associated depression development.
UNASSIGNED: Our findings suggest a bidirectional causal relationship between CRS and depression, offering a new perspective on the association between CRS and depression.
摘要：
■慢性鼻窦炎（CRS）与抑郁症之间的因果关系尚不清楚。在此，我们采用孟德尔随机化（MR）结合单细胞分析来研究CRS和抑郁症之间的因果关系。
■与CRS和抑郁症有关的数据是从全基因组关联研究数据库中挖掘的，单细胞数据集来自文献。为了探索因果关系，我们使用MR-Egger进行了双向MR分析，加权中位数，逆方差加权(IVW)，简单模式，和加权模式，IVW代表最重要的方法。Further,进行敏感性分析以评估MR分析结果的稳健性.通过单细胞组合MR分析分析候选基因。
■前向MR分析显示，当抑郁是暴露因素，CRS是结果时，抑郁是CRS的危险因素（OR=1.425，P<0.001）。反向MR分析显示，当CRS是暴露因素，抑郁是结果时，CRS与抑郁之间存在相同的正相关关系（OR=1.012，P=0.038）。灵敏度分析验证了双向MR分析结果的鲁棒性。十种细胞类型（内皮细胞，纤毛,基底,髓样，桅杆,顶端,等离子体,腺体,成纤维细胞,和T细胞）在单细胞数据集中鉴定。受体-配体对的网络表明，在正常样本中，细胞间的相互作用存在于各种细胞类型之间，如上皮，桅杆,髓样，和内皮细胞。相比之下,CRS样本只有一个特定的受体-配体对，局限于骨髓细胞。TCF4和MEF2C对于CRS相关抑郁症的发展可能至关重要。
■我们的研究结果表明CRS与抑郁症之间存在双向因果关系，为CRS与抑郁症之间的关联提供了新的视角。
■与CRS和抑郁症有关的数据是从全基因组关联研究数据库中挖掘的，单细胞数据集来自文献。为了探索因果关系，我们使用MR-Egger进行了双向MR分析，加权中位数，逆方差加权(IVW)，简单模式，和加权模式，IVW代表最重要的方法。Further,进行敏感性分析以评估MR分析结果的稳健性.通过单细胞组合MR分析分析候选基因。
■前向MR分析显示，当抑郁是暴露因素，CRS是结果时，抑郁是CRS的危险因素（OR=1.425，P<0.001）。反向MR分析显示，当CRS是暴露因素，抑郁是结果时，CRS与抑郁之间存在相同的正相关关系（OR=1.012，P=0.038）。灵敏度分析验证了双向MR分析结果的鲁棒性。十种细胞类型（内皮细胞，纤毛,基底,髓样，桅杆,顶端,等离子体,腺体,成纤维细胞,和T细胞）在单细胞数据集中鉴定。受体-配体对的网络表明，在正常样本中，细胞间的相互作用存在于各种细胞类型之间，如上皮，桅杆,髓样，和内皮细胞。相比之下,CRS样本只有一个特定的受体-配体对，局限于骨髓细胞。TCF4和MEF2C对于CRS相关抑郁症的发展可能至关重要。
■我们的研究结果表明CRS与抑郁症之间存在双向因果关系，为CRS与抑郁症之间的关联提供了新的视角。
