目的 支氣管哮喘是嚴(yán)重影響全球公眾健康的重大慢病之一，通過使用GEO數(shù)據(jù)集和孟德爾隨機(jī)化方法確定哮喘新的遺傳靶點(diǎn)，為臨床治療和機(jī)制研究提供依據(jù)。方法 通過基因表達(dá)綜合數(shù)據(jù)庫(kù)（GEO）獲得相關(guān)數(shù)據(jù)集，獲得數(shù)據(jù)后進(jìn)行差異基因的表達(dá)數(shù)量性狀位點(diǎn)（expression quantitative trait locus，eQTL）分析和孟德爾隨機(jī)化（mendelian randomization，MR）分析，確定潛在靶點(diǎn)；再通過基因集合富集分析（gene set enrichment analysis，GSEA）和基因本體論（gene ontology，GO）/京都基因和基因組百科全書（Kyoto encyclopedia of genes and genomes，KEGG）富集分析來探索這些基因的功能和富集通路；通過免疫浸潤(rùn)方法探索靶點(diǎn)與相關(guān)免疫細(xì)胞的關(guān)聯(lián)；利用醫(yī)學(xué)本體信息檢索平臺(tái)Coremine Medical數(shù)據(jù)庫(kù)，篩選核心基因相關(guān)治療中藥并進(jìn)行歸納分析，最后設(shè)立外部驗(yàn)證集進(jìn)行驗(yàn)證。結(jié)果 共鑒定出280個(gè)高表達(dá)基因和1 127個(gè)低表達(dá)基因；MR分析確定了12個(gè)與哮喘顯著相關(guān)的核心基因靶點(diǎn)：PGAP3、FAM177A1、UGDH、AASDH、CREB1、ZNF429、CCNG2、SKAP2、ANKRD10、DR1、ISOC1以及LPAR6；預(yù)測(cè)出人參、五味子、麻黃、杜仲、北沙參等67味靶向中藥，主要涉及補(bǔ)虛藥、活血化瘀藥；MR分析結(jié)果與外部驗(yàn)證集的結(jié)果一致，強(qiáng)調(diào)了本研究的可靠性。結(jié)論 篩選并驗(yàn)證了12個(gè)哮喘潛在靶點(diǎn)，并對(duì)相關(guān)干預(yù)中藥進(jìn)行了預(yù)測(cè)，為進(jìn)一步深入探究哮喘的發(fā)病機(jī)制、早期篩查診斷、早期預(yù)防、靶向治療以及中醫(yī)藥臨床診療提供了新的線索。

Objective Bronchial asthma is one of the major chronic diseases that seriously affects public health worldwide. This study aims to identify new genetic targets for asthma by using GEO datasets and mendelian randomization (MR) methods, providing a basis for clinical treatment and mechanism studies. Methods The relevant datasets were obtained through the Gene Expression Omnibus (GEO) database, and after obtaining the data, the expression quantitative trait locus (eQTL) analysis and MR analysis were performed to identify potential targets; the functional roles and pathways of these genes were explored through gene set enrichment analysis (GSEA) and gene ontology (GO)/Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, and the associations of the targets with relevant immune cells were explored through immune infiltration methods, and core genes were screened through Coremine medical database, which was a platform for medical ontology information retrieval. Coremine medical database to screen core gene-related therapeutic herbal medicines and generalize and analyze them, and finally set up an external validation set for confirmation. Results A total of 280 highly-expressed and 1 127 low-expressed genes were identified. MR analysis identified 12 core genes significantly associated with asthma, which includes PGAP3, FAM177A1, UGDH, AASDH, CREB1, ZNF429, CCNG2, SKAP2, ANKRD10, DR1, ISOC1, and LPAR6; Additionally, 67 traditional Chinese medicines (TCMs) were predicted, including Renshen (Ginseng Radix et Rhizoma), Wuweizi (Schisandrae Chinensis Fructus), Mahuang (Ephedrae Herba), Duzhong (Eucommiae Cortex), and Beishashen (Glehniae Radix), which were mainly involved in the categories of deficiency tonic, blood circulation and blood stasis removing medicines; The MR analysis results were consistent with those of the external validation set, which emphasized the reliability of the present study. Conclusion The present study screened and validated 12 potential asthma targets and predicted the related TCMs, which provides new insights into asthma pathogenesis, early screening, targeted therapy, and the clinical application of TCMs.

Q811.4;R285

國(guó)家自然科學(xué)基金項(xiàng)目（82474483）;國(guó)家重點(diǎn)研發(fā)計(jì)劃（2023YFC3502602，2023YFC3502600）;河南省高?？萍紕?chuàng)新團(tuán)隊(duì)（23IRTSTHN027）;國(guó)家中醫(yī)臨床研究基地科研專項(xiàng)（2022JDZX046）;河南省科技攻關(guān)項(xiàng)目（232102310472）;河南省中醫(yī)藥科學(xué)研究專項(xiàng)（2022ZY1047）