【作者】 陈哲；

【导师】 王翔；

【作者基本信息】 中南大学 ， 临床医学（专业学位）， 2025， 硕士

【摘要】 目的本研究旨在探讨多种呼吸系统疾病之间的共同遗传基础,识别其共享的分子机制与生物学通路,探索肺癌、哮喘、慢性阻塞性肺疾病、特发性肺纤维化和鼾症这五种常见呼吸系统疾病是否存在关联及共病机制,为进一步寻找潜在的干预策略提供理论支持。方法本研究是一项全基因组范围的多效性关联研究,通过多种统计方法系统性地评估哮喘、慢性阻塞性肺疾病、特发性肺纤维化、肺癌和鼾症这五种常见呼吸系统疾病之间的遗传关联。研究依托当前公开可获取的、规模最大的全基因组关联研究汇总数据,从全球和局部两个层面评估遗传相关性,识别潜在的多效性位点,并结合多组学数据进行功能注释和通路分析。同时,运用孟德尔随机化方法探讨这些疾病之间的潜在因果关系。结果在5种呼吸系统疾病之间,共10个配对性状均存在显著的遗传关联,多性状关联分析鉴定了12400个显著的潜在多效性单核苷酸多态性,经注释后得到156个独立多效性位点。此外,多性状共定位分析确定了15个共定位位点,并确定了共定位性状子集。基于基因的分析鉴定了678个潜在的多效性基因,并且进一步在转录组和蛋白质水平进行验证。通路富集及单细胞富集分析均支持免疫系统在呼吸疾病中的作用。此外,孟德尔随机化分析揭示了部分呼吸系统疾病之间可能存在的潜在因果关联。结论此研究揭示了呼吸疾病之间的共同遗传基础和多效性基因。发现免疫系统在呼吸疾病共病中具有重要生物学作用。为呼吸疾病共病现象提供进一步的治疗策略及风险预测提供理论证据。图5幅,表7个,参考文献59篇更多还原

【Abstract】 ObjectiveThis study aims to investigate the shared genetic basis among various respiratory diseases,identify their common molecular mechanisms and biological pathways,and explore potential associations and comorbid mechanisms among five common respiratory conditions—lung cancer,asthma,chronic obstructive pulmonary disease(COPD),idiopathic pulmonary fibrosis(IPF)and snoring,to provide theoretical support for the development of potential intervention strategies.MethodsWe conducted a genome-wide pleiotropy association study to systematically assess the genetic correlations among five common respiratory diseases:asthma,chronic obstructive pulmonary disease,idiopathic pulmonary fibrosis,lung cancer,and snoring.Leveraging the largest publicly available genome-wide association study summary statistics,we evaluated both global and local genetic correlations,identified potential pleiotropic loci,and performed functional annotation and pathway analysis using multi-omics data.Furthermore,Mendelian randomization was applied to explore potential causal relationships between these diseases.ResultsSignificant genetic correlations were observed among all ten disease pairs.A total of 12400 genome-wide significant pleiotropic single nucleotide polymorphisms were identified,corresponding to 156independent pleiotropic loci after annotation.Multi-trait colocalization analysis revealed 15 colocalized loci and defined distinct colocalization trait subsets.Gene-based analysis identified 678 candidate pleiotropic genes,which were further validated at transcriptomic and proteomic levels.Enrichment analyses highlighted the pivotal role of immune-related pathways,supported by single-cell level evidence.MR analysis suggested potential causal associations between some of the studied respiratory diseases.ConclusionThis study reveals the shared genetic basis and pleiotropic genes among respiratory diseases,and identifies the immune system as playing a critical biological role in their comorbidity.These findings provide theoretical evidence to support the development of therapeutic strategies and risk prediction for respiratory disease comorbidity.更多还原