PDF(Pubmed)
Abstract：
BACKGROUND: Neuropsychiatric disorders and cervical cancer exert substantial influences on women\'s health. Furthermore, neuropsychiatric disorders frequently manifest as common symptoms in cancer patients, potentially increasing the risk of malignant neoplasms. This study aimed to identify neuropsychiatric disorders that are genetically and causally related to cervical cancer and to investigate the molecular mechanisms underlying these associations.
METHODS: GWAS data related to nine neuropsychiatric disorders, namely, schizophrenia, bipolar disorder, autism spectrum disorder, Parkinson\'s disease, anxiety, Alzheimer\'s disease, mood disorders, depression, and alcohol dependence, were obtained to calculate heritability (h2) and genetic correlation (rg) with cervical cancer using linkage disequilibrium score regression (LDSC). Mendelian randomization (MR) analysis of the two cohorts was employed to assess the causal effects. Shared gene expression pattern analysis was subsequently conducted to investigate the molecular mechanism underlying these significant associations.
RESULTS: Anxiety, mood disorders, depression, and alcohol dependence were genetically correlated with cervical cancer (all adjusted P < 0.05). Only depression was causally related to cervical cancer in both the discovery (ORIVW: 1.41, PIVW = 0.02) and replication cohorts (ORIVW: 1.80, PIVW = 0.03) in the MR analysis. Gene expression pattern analysis revealed that 270 genes related to depression and cervical cancer, including tumour necrosis factor (TNF), were significantly upregulated in cervical cancer patients, while vascular endothelial growth factor A (VEGFA), transcription factor AP-1 (JUN), and insulin-like growth factor I (IGF-I) were associated with prognosis in cervical cancer patients (all P < 0.05). These overlapping genes implicated the involvement of multiple biological mechanisms, such as neuron death, the PI3K-Akt signalling pathway, and human papillomavirus infection.
CONCLUSIONS: Genetic, causal and molecular evidence indicates that depression increases the risk of cervical cancer. The TNF, VEGFA, JUN, and IGF-1 genes and the neuron death, PI3K-Akt, and human papillomavirus infection signalling pathways may possibly explain this association.
METHODS: GWAS data related to nine neuropsychiatric disorders, namely, schizophrenia, bipolar disorder, autism spectrum disorder, Parkinson\'s disease, anxiety, Alzheimer\'s disease, mood disorders, depression, and alcohol dependence, were obtained to calculate heritability (h2) and genetic correlation (rg) with cervical cancer using linkage disequilibrium score regression (LDSC). Mendelian randomization (MR) analysis of the two cohorts was employed to assess the causal effects. Shared gene expression pattern analysis was subsequently conducted to investigate the molecular mechanism underlying these significant associations.
RESULTS: Anxiety, mood disorders, depression, and alcohol dependence were genetically correlated with cervical cancer (all adjusted P < 0.05). Only depression was causally related to cervical cancer in both the discovery (ORIVW: 1.41, PIVW = 0.02) and replication cohorts (ORIVW: 1.80, PIVW = 0.03) in the MR analysis. Gene expression pattern analysis revealed that 270 genes related to depression and cervical cancer, including tumour necrosis factor (TNF), were significantly upregulated in cervical cancer patients, while vascular endothelial growth factor A (VEGFA), transcription factor AP-1 (JUN), and insulin-like growth factor I (IGF-I) were associated with prognosis in cervical cancer patients (all P < 0.05). These overlapping genes implicated the involvement of multiple biological mechanisms, such as neuron death, the PI3K-Akt signalling pathway, and human papillomavirus infection.
CONCLUSIONS: Genetic, causal and molecular evidence indicates that depression increases the risk of cervical cancer. The TNF, VEGFA, JUN, and IGF-1 genes and the neuron death, PI3K-Akt, and human papillomavirus infection signalling pathways may possibly explain this association.
摘要：
背景：神经精神疾病和宫颈癌对妇女的健康产生重大影响。此外，神经精神疾病通常表现为癌症患者的常见症状，可能增加恶性肿瘤的风险。这项研究旨在确定与宫颈癌遗传和因果关系相关的神经精神疾病，并研究这些关联的分子机制。
方法：与九种神经精神疾病相关的GWAS数据，即,精神分裂症,双相情感障碍,自闭症谱系障碍，帕金森病,焦虑,老年痴呆症,情绪障碍,抑郁症,和酒精依赖，获得了使用连锁不平衡评分回归（LDSC）计算遗传度（h2）和与宫颈癌的遗传相关性（rg）。采用两个队列的孟德尔随机化（MR）分析来评估因果效应。随后进行共享基因表达模式分析以研究这些重要关联的分子机制。
结果：焦虑，情绪障碍,抑郁症,酒精依赖与宫颈癌遗传相关(均校正P<0.05)。在MR分析中，在发现（ORIVW：1.41，PIVW=0.02）和复制队列（ORIVW：1.80，PIVW=0.03）中，只有抑郁症与宫颈癌有因果关系。基因表达模式分析显示270个与抑郁症和宫颈癌相关的基因,包括肿瘤坏死因子（TNF），在宫颈癌患者中显著上调，而血管内皮生长因子A(VEGFA),转录因子AP-1(JUN),胰岛素样生长因子I(IGF-I)与宫颈癌患者预后相关(均P<0.05)。这些重叠的基因牵涉到多种生物学机制，比如神经元死亡，PI3K-Akt信号通路，和人乳头瘤病毒感染。
结论：遗传，因果关系和分子证据表明，抑郁症会增加宫颈癌的风险。TNF，VEGFA,JUN,IGF-1基因和神经元死亡，PI3K-Akt,和人乳头瘤病毒感染信号通路可能解释这种关联。
方法：与九种神经精神疾病相关的GWAS数据，即,精神分裂症,双相情感障碍,自闭症谱系障碍，帕金森病,焦虑,老年痴呆症,情绪障碍,抑郁症,和酒精依赖，获得了使用连锁不平衡评分回归（LDSC）计算遗传度（h2）和与宫颈癌的遗传相关性（rg）。采用两个队列的孟德尔随机化（MR）分析来评估因果效应。随后进行共享基因表达模式分析以研究这些重要关联的分子机制。
结果：焦虑，情绪障碍,抑郁症,酒精依赖与宫颈癌遗传相关(均校正P<0.05)。在MR分析中，在发现（ORIVW：1.41，PIVW=0.02）和复制队列（ORIVW：1.80，PIVW=0.03）中，只有抑郁症与宫颈癌有因果关系。基因表达模式分析显示270个与抑郁症和宫颈癌相关的基因,包括肿瘤坏死因子（TNF），在宫颈癌患者中显著上调，而血管内皮生长因子A(VEGFA),转录因子AP-1(JUN),胰岛素样生长因子I(IGF-I)与宫颈癌患者预后相关(均P<0.05)。这些重叠的基因牵涉到多种生物学机制，比如神经元死亡，PI3K-Akt信号通路，和人乳头瘤病毒感染。
结论：遗传，因果关系和分子证据表明，抑郁症会增加宫颈癌的风险。TNF，VEGFA,JUN,IGF-1基因和神经元死亡，PI3K-Akt,和人乳头瘤病毒感染信号通路可能解释这种关联。
