揭示肠道微生物群和哮喘之间的遗传联系：孟德尔随机化
2024/10/29
摘要
背景：多项研究提示，肠道微生物组和哮喘之间存在潜在关联。我们的目标是使用先进的遗传和宏基因组技术来阐明肠道菌群和哮喘之间的因果关系和潜在机制。
方法：本研究利用可公开获取的全基因组关联研究（GWAS），利用连锁不平衡评分回归（LDSC）和孟德尔随机化（MR）分析来研究119个肠道菌群与哮喘之间的关系。荟萃分析综合了从LDSC、正向MR和反向MR获得的汇总效应估计值。纳入18,340人的MiBioGen合作项目确定了与肠道细菌相关的遗传变异。我们从英国生物样本库（UK Biobank）、FinnGen和GERA收集了哮喘数据，共包括82,060例患者和641,049例对照。
结果：LDSC分析显示哮喘与RuminococcaceaeUCG004（Rg=−0.55,p=7.66×10−5）和Subdoligranulum （Rg=−0.35,p=3.61×10−4）呈显著负相关。正向MR分析提示，丁酸球菌（OR=0.92, p=0.01）、Turicibacter（OR=0.95,p=0.025）、丁酸弧菌（OR=0.98,p=0.047）与降低哮喘风险有关。相反,粪球菌属2（OR=1.10,p=0.035）和玫瑰球菌属（OR=1.07,p=0.039）与风险增加相关。反向MR分析显示，遗传预测的哮喘与嗜木聚糖真杆菌组（Beta=−0.08,p=9.25×10−7）、LachnospiraceaeNK4A136组（Beta =−0.05,p = 1.26×10−4）和艾森伯格菌属（Beta=0.06,p=0.015,Rg_P=0.043）显著相关。
结论：研究结果强调了特定肠道微生物群与哮喘之间的显著遗传相关性和因果关系。这些见解强调了肠道微生物作为哮喘风险标志物和调节剂的潜力，为靶向治疗策略提供了新的途径。
Unveiling genetic links between gut microbiota and asthma: a Mendelian randomization
X. W. Zheng, M. B. Chen, Y. Zhuang, L. Zhao, Y. J. Qian and C. C. Shi
Abstract
BACKGROUND:Multiple studies suggest a potential connection between the gut microbiome and asthma. Our objective is to use advanced genetic and metagenomic techniques to elucidate the causal relationships and underlying mechanisms between gut microbiota and asthma.
METHODS:The study utilized comprehensive Linkage Disequilibrium Score Regression (LDSC) and Mendelian randomization (MR) analyses to examine the relationship between 119 gut microbiota genera and asthma, using publicly accessible genome-wide association studies (GWAS). The meta-analysis synthesized summary effect estimates obtained from LDSC, forward MR, and reverse MR. The MiBioGen collaboration, involving 18,340 individuals, identified genetic variations associated with gut bacteria. Asthma data were collected from the UK Biobank, FinnGen, and GERA, encompassing a total of 82,060 cases and 641,049 controls.
RESULTS:LDSC analysis revealed significant negative genetic correlations between asthma and RuminococcaceaeUCG004 (Rg = −0.55, p = 7.66 × 10−5) and Subdoligranulum (Rg = −0.35, p = 3.61 × 10−4). Forward MR analysis suggested associations between Butyricicoccus (OR = 0.92, p = 0.01), Turicibacter (OR = 0.95, p = 0.025), Butyrivibrio (OR = 0.98, p = 0.047), and reduced asthma risk. Conversely, Coprococcus2 (OR = 1.10, p = 0.035) and Roseburia (OR = 1.07, p = 0.039) were associated with increased risk. Reverse MR analysis indicated significant associations between genetically predicted asthma and Eubacteriumxylanophilum group (Beta = −0.08,p = 9.25 × 10−7), LachnospiraceaeNK4A136 group (Beta = −0.05, p = 1.26 × 10−4), and Eisenbergiella (Beta = 0.06, p = 0.015, Rg_P = 0.043).
CONCLUSION:The findings underscore significant genetic correlations and causal relationships between specific gut microbiota and asthma. These insights highlight the potential of gut microbiota as both markers and modulators of asthma risk, offering new avenues for targeted therapeutic strategies.
背景：多项研究提示，肠道微生物组和哮喘之间存在潜在关联。我们的目标是使用先进的遗传和宏基因组技术来阐明肠道菌群和哮喘之间的因果关系和潜在机制。
方法：本研究利用可公开获取的全基因组关联研究（GWAS），利用连锁不平衡评分回归（LDSC）和孟德尔随机化（MR）分析来研究119个肠道菌群与哮喘之间的关系。荟萃分析综合了从LDSC、正向MR和反向MR获得的汇总效应估计值。纳入18,340人的MiBioGen合作项目确定了与肠道细菌相关的遗传变异。我们从英国生物样本库（UK Biobank）、FinnGen和GERA收集了哮喘数据，共包括82,060例患者和641,049例对照。
结果：LDSC分析显示哮喘与RuminococcaceaeUCG004（Rg=−0.55,p=7.66×10−5）和Subdoligranulum （Rg=−0.35,p=3.61×10−4）呈显著负相关。正向MR分析提示，丁酸球菌（OR=0.92, p=0.01）、Turicibacter（OR=0.95,p=0.025）、丁酸弧菌（OR=0.98,p=0.047）与降低哮喘风险有关。相反,粪球菌属2（OR=1.10,p=0.035）和玫瑰球菌属（OR=1.07,p=0.039）与风险增加相关。反向MR分析显示，遗传预测的哮喘与嗜木聚糖真杆菌组（Beta=−0.08,p=9.25×10−7）、LachnospiraceaeNK4A136组（Beta =−0.05,p = 1.26×10−4）和艾森伯格菌属（Beta=0.06,p=0.015,Rg_P=0.043）显著相关。
结论：研究结果强调了特定肠道微生物群与哮喘之间的显著遗传相关性和因果关系。这些见解强调了肠道微生物作为哮喘风险标志物和调节剂的潜力，为靶向治疗策略提供了新的途径。
（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）
（Frontiers in Microbiology 2024 Vol. 15 DOI: ARTN 144862910.3389/fmicb.2024.1448629）
（Frontiers in Microbiology 2024 Vol. 15 DOI: ARTN 144862910.3389/fmicb.2024.1448629）
Unveiling genetic links between gut microbiota and asthma: a Mendelian randomization
X. W. Zheng, M. B. Chen, Y. Zhuang, L. Zhao, Y. J. Qian and C. C. Shi
Abstract
BACKGROUND:Multiple studies suggest a potential connection between the gut microbiome and asthma. Our objective is to use advanced genetic and metagenomic techniques to elucidate the causal relationships and underlying mechanisms between gut microbiota and asthma.
METHODS:The study utilized comprehensive Linkage Disequilibrium Score Regression (LDSC) and Mendelian randomization (MR) analyses to examine the relationship between 119 gut microbiota genera and asthma, using publicly accessible genome-wide association studies (GWAS). The meta-analysis synthesized summary effect estimates obtained from LDSC, forward MR, and reverse MR. The MiBioGen collaboration, involving 18,340 individuals, identified genetic variations associated with gut bacteria. Asthma data were collected from the UK Biobank, FinnGen, and GERA, encompassing a total of 82,060 cases and 641,049 controls.
RESULTS:LDSC analysis revealed significant negative genetic correlations between asthma and RuminococcaceaeUCG004 (Rg = −0.55, p = 7.66 × 10−5) and Subdoligranulum (Rg = −0.35, p = 3.61 × 10−4). Forward MR analysis suggested associations between Butyricicoccus (OR = 0.92, p = 0.01), Turicibacter (OR = 0.95, p = 0.025), Butyrivibrio (OR = 0.98, p = 0.047), and reduced asthma risk. Conversely, Coprococcus2 (OR = 1.10, p = 0.035) and Roseburia (OR = 1.07, p = 0.039) were associated with increased risk. Reverse MR analysis indicated significant associations between genetically predicted asthma and Eubacteriumxylanophilum group (Beta = −0.08,p = 9.25 × 10−7), LachnospiraceaeNK4A136 group (Beta = −0.05, p = 1.26 × 10−4), and Eisenbergiella (Beta = 0.06, p = 0.015, Rg_P = 0.043).
CONCLUSION:The findings underscore significant genetic correlations and causal relationships between specific gut microbiota and asthma. These insights highlight the potential of gut microbiota as both markers and modulators of asthma risk, offering new avenues for targeted therapeutic strategies.
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