通过孟德尔随机化，蛋白质组学分析揭示了儿童哮喘的潜在治疗靶点
2024/06/26
摘要
背景：哮喘是儿童中最常见的慢性疾病，对他们的健康构成严重威胁。本研究旨在评估各种血浆蛋白与儿童哮喘之间的关系，从而确定潜在的治疗目标。
方法：根据公开的全基因组关联研究摘要统计，我们采用了双样本孟德尔随机化（MR）方法来阐明血浆蛋白与哮喘之间的因果关系。然后进行中介分析，评估血浆蛋白通过风险因素对儿童哮喘的间接影响。此外，还利用英国生物库数据集进行了综合分析，以探讨血浆蛋白与各种表型之间的关联。
结果：MR分析发现了10种血浆蛋白与儿童哮喘之间的因果关系。七种蛋白质（TLR4、UBP25、CBR1、Rac GTPase-activating protein 1 [RGAP1]、IL-21、MICB和PDE4D）水平的升高和三种蛋白质（GSTO1、LIRB4和PIGF）水平的降低与儿童哮喘风险的增加有关。我们的研究结果进一步验证了所报告的风险因素（体重指数、情绪波动、花粉热或过敏性鼻炎、湿疹或皮炎）与儿童哮喘之间的联系。中介分析揭示了蛋白质通过风险因素对儿童哮喘结果的影响。此外，MR分析还发现73种血浆蛋白与至少一种儿童哮喘风险因素存在因果关系。其中，RGAP1通过湿疹或皮炎介导了儿童哮喘风险的很大一部分（25.10%）。最后，基于这10种蛋白质和1403种疾病的表型关联研究提供了这些生物标记物与多种表型之间的新关联。
结论：我们的研究全面探讨了血浆蛋白与儿童哮喘之间的因果关系，为潜在的治疗靶点提供了新的见解。
Proteomic analysis reveals potential therapeutic targets for childhood asthma through Mendelian randomization
Y. Q. Wu, Y. X. Cai, X. L. Chen, S. Q. Chen, X. F. Huang and Z. L. Lin
Abstract
BACKGRUND:Asthma is the most common chronic disease among children and poses a significant threat to their health. This study aims to assess the relationship between various plasma proteins and childhood asthma, thereby identifying potential therapeutic targets.
METHODS: Based on publicly available genome-wide association study summary statistics, we employed a two-sample Mendelian randomization (MR) approach to elucidate the causal relationship between plasma proteins and asthma. Mediation analysis was then conducted to evaluate the indirect influence of plasma proteins on childhood asthma mediated through risk factors. Comprehensive analysis was also conducted to explore the association between plasma proteins and various phenotypes using the UK Biobank dataset.
RESULTS: MR analysis uncovered a causal relationship between 10 plasma proteins and childhood asthma. Elevated levels of seven proteins (TLR4, UBP25, CBR1, Rac GTPase-activating protein 1 [RGAP1], IL-21, MICB, and PDE4D) and decreased levels of three proteins (GSTO1, LIRB4 and PIGF) were associated with an increased risk of childhood asthma. Our findings further validated the connections between reported risk factors (body mass index, mood swings, hay fever or allergic rhinitis, and eczema or dermatitis) and childhood asthma. Mediation analysis revealed the influence of proteins on childhood asthma outcomes through risk factors. Furthermore, the MR analysis identified 73 plasma proteins that exhibited causal associations with at least one risk factor for childhood asthma. Among them, RGAP1 mediates a significant proportion (25.10%) of the risk of childhood asthma through eczema or dermatitis. Finally, a phenotype-wide association study based on these 10 proteins and 1403 diseases provided novel associations between these biomarkers and multiple phenotypes.
CONCLUSIONS: Our study comprehensively investigated the causal relationship between plasma proteins and childhood asthma, providing novel insights into potential therapeutic targets.
背景：哮喘是儿童中最常见的慢性疾病，对他们的健康构成严重威胁。本研究旨在评估各种血浆蛋白与儿童哮喘之间的关系，从而确定潜在的治疗目标。
方法：根据公开的全基因组关联研究摘要统计，我们采用了双样本孟德尔随机化（MR）方法来阐明血浆蛋白与哮喘之间的因果关系。然后进行中介分析，评估血浆蛋白通过风险因素对儿童哮喘的间接影响。此外，还利用英国生物库数据集进行了综合分析，以探讨血浆蛋白与各种表型之间的关联。
结果：MR分析发现了10种血浆蛋白与儿童哮喘之间的因果关系。七种蛋白质（TLR4、UBP25、CBR1、Rac GTPase-activating protein 1 [RGAP1]、IL-21、MICB和PDE4D）水平的升高和三种蛋白质（GSTO1、LIRB4和PIGF）水平的降低与儿童哮喘风险的增加有关。我们的研究结果进一步验证了所报告的风险因素（体重指数、情绪波动、花粉热或过敏性鼻炎、湿疹或皮炎）与儿童哮喘之间的联系。中介分析揭示了蛋白质通过风险因素对儿童哮喘结果的影响。此外，MR分析还发现73种血浆蛋白与至少一种儿童哮喘风险因素存在因果关系。其中，RGAP1通过湿疹或皮炎介导了儿童哮喘风险的很大一部分（25.10%）。最后，基于这10种蛋白质和1403种疾病的表型关联研究提供了这些生物标记物与多种表型之间的新关联。
结论：我们的研究全面探讨了血浆蛋白与儿童哮喘之间的因果关系，为潜在的治疗靶点提供了新的见解。
（中日友好医院呼吸与危重症医学科 李春晓 摘译 林江涛 审校）
（Clinical and Translational Allergy 2024 Vol. 14 Issue 5 DOI: ARTN e1235710.1002/clt2.12357）
（Clinical and Translational Allergy 2024 Vol. 14 Issue 5 DOI: ARTN e1235710.1002/clt2.12357）
Proteomic analysis reveals potential therapeutic targets for childhood asthma through Mendelian randomization
Y. Q. Wu, Y. X. Cai, X. L. Chen, S. Q. Chen, X. F. Huang and Z. L. Lin
Abstract
BACKGRUND:Asthma is the most common chronic disease among children and poses a significant threat to their health. This study aims to assess the relationship between various plasma proteins and childhood asthma, thereby identifying potential therapeutic targets.
METHODS: Based on publicly available genome-wide association study summary statistics, we employed a two-sample Mendelian randomization (MR) approach to elucidate the causal relationship between plasma proteins and asthma. Mediation analysis was then conducted to evaluate the indirect influence of plasma proteins on childhood asthma mediated through risk factors. Comprehensive analysis was also conducted to explore the association between plasma proteins and various phenotypes using the UK Biobank dataset.
RESULTS: MR analysis uncovered a causal relationship between 10 plasma proteins and childhood asthma. Elevated levels of seven proteins (TLR4, UBP25, CBR1, Rac GTPase-activating protein 1 [RGAP1], IL-21, MICB, and PDE4D) and decreased levels of three proteins (GSTO1, LIRB4 and PIGF) were associated with an increased risk of childhood asthma. Our findings further validated the connections between reported risk factors (body mass index, mood swings, hay fever or allergic rhinitis, and eczema or dermatitis) and childhood asthma. Mediation analysis revealed the influence of proteins on childhood asthma outcomes through risk factors. Furthermore, the MR analysis identified 73 plasma proteins that exhibited causal associations with at least one risk factor for childhood asthma. Among them, RGAP1 mediates a significant proportion (25.10%) of the risk of childhood asthma through eczema or dermatitis. Finally, a phenotype-wide association study based on these 10 proteins and 1403 diseases provided novel associations between these biomarkers and multiple phenotypes.
CONCLUSIONS: Our study comprehensively investigated the causal relationship between plasma proteins and childhood asthma, providing novel insights into potential therapeutic targets.
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肥大细胞通过前列腺素E2驱动的可溶性ST2控制肺2型炎症
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