衰弱与慢性阻塞性肺病或哮喘之间的因果关系：双向孟德尔随机抽样研究
2024/02/23
摘要
背景：观察性研究已经确定了衰弱和慢性阻塞性肺疾病之间的强烈关联。然而，这种关联的因果性质仍不清楚。为了填补这一空白，我们进行了一项双向孟德尔随机化（MR）研究，以调查以衰弱为测量标准的衰弱指数（FI）与慢性阻塞性肺疾病（COPD）或哮喘之间的因果关系。
方法：最新的针对FI的基因组关联研究的meta分析包括来自UK Biobank和TwinGene的欧洲血统个体（N = 175,226），分析得出了衰弱的遗传仪器和结果摘要统计数据。 COPD和哮喘的遗传仪器以及结果摘要数据来自FinnGen对欧洲血统个体进行的全球基因组研究，其中COPD的样本量为16,410例病例和283,589例对照，哮喘的样本量为37,253例病例和187,112例对照。MR分析采用逆方差加权（IVW）方法进行，辅以加权中位数方法、MR-Egger回归和MR杂合性残差和异常值（MR-PRESSO）检验。
结果：我们的结果显示，遗传预测的更高FI与增加COPD（比值比[OR] 1.75，95％置信区间[CI] 1.29-2.36）和哮喘（OR 2.10，95％CI 1.44-3.16）的风险显着相关。在反向分析中， COPD（β 0.06，95％CI 0.01-0.10）和哮喘（β 0.08，95％CI 0.06-0.11）的遗传易感性都显示出与更高FI显着相关的关联。
结论：我们的研究强化了支持衰弱与阻塞性肺疾病之间相互因果关系的现有证据。对这种相互联系的更深入理解对于阻塞性肺疾病的预防和治疗至关重要。
Causal relationship between frailty and chronic obstructive pulmonary disease or asthma: A two sample bidirectional Mendelian randomization study
Qu J, Liang Y, Rao Y, Pei Y, Li D, Zhang Y, Chen Y, Sun Y
Abstract
Background:Observational studies have established a strong association between frailty and obstructive lung diseases. However, the causal nature of this association remains unclear. To address this gap, we conducted a bidirectional Mendelian randomization (MR) study to investigate the causal relationship between frailty, as measured by the frailty index (FI), and chronic obstructive pulmonary disease (COPD) or asthma.
Methods:The latest meta-analysis of genome-wide association studies for FI, which included individuals of European ancestry from UK Biobank and TwinGene (N = 175,226), yielded the genetic instruments for frailty and outcome summary statistics. The genetic instrument for COPD and asthma, as well as the outcome summary data, were derived from the GWAS conducted on individuals of European ancestry from the FinnGen, with a sample size of 16,410 cases and 283,589 controls for COPD, and 37,253 cases and 187,112 controls for asthma. The analysis of MR was conducted employing the inverse-variance weighted (IVW) method, complemented by the weighted median method, MR-Egger regression, and MR pleiotropy residual sum and outlier (MR-PRESSO) test.
Results:Our results showed that genetically predicted higher FI was significantly associated with increased risk of COPD (odds ratio [OR] 1.75, 95 % confidence interval [CI] 1.29-2.36) and asthma (OR 2.10, 95 % CI 1.44-3.16). In the reverse direction analysis, genetic liability to both COPD (beta 0.06, 95 % CI 0.01-0.10) and asthma (beta 0.08, 95 % CI 0.06-0.11) showed significant associations with a higher FI.
Conclusion:Our research has reinforced the existing evidence supporting a reciprocal causal relationship between frailty and obstructive lung diseases. A deeper comprehension of this interconnection is imperative for the prevention and treatment of obstructive lung diseases.
背景：观察性研究已经确定了衰弱和慢性阻塞性肺疾病之间的强烈关联。然而，这种关联的因果性质仍不清楚。为了填补这一空白，我们进行了一项双向孟德尔随机化（MR）研究，以调查以衰弱为测量标准的衰弱指数（FI）与慢性阻塞性肺疾病（COPD）或哮喘之间的因果关系。
方法：最新的针对FI的基因组关联研究的meta分析包括来自UK Biobank和TwinGene的欧洲血统个体（N = 175,226），分析得出了衰弱的遗传仪器和结果摘要统计数据。 COPD和哮喘的遗传仪器以及结果摘要数据来自FinnGen对欧洲血统个体进行的全球基因组研究，其中COPD的样本量为16,410例病例和283,589例对照，哮喘的样本量为37,253例病例和187,112例对照。MR分析采用逆方差加权（IVW）方法进行，辅以加权中位数方法、MR-Egger回归和MR杂合性残差和异常值（MR-PRESSO）检验。
结果：我们的结果显示，遗传预测的更高FI与增加COPD（比值比[OR] 1.75，95％置信区间[CI] 1.29-2.36）和哮喘（OR 2.10，95％CI 1.44-3.16）的风险显着相关。在反向分析中， COPD（β 0.06，95％CI 0.01-0.10）和哮喘（β 0.08，95％CI 0.06-0.11）的遗传易感性都显示出与更高FI显着相关的关联。
结论：我们的研究强化了支持衰弱与阻塞性肺疾病之间相互因果关系的现有证据。对这种相互联系的更深入理解对于阻塞性肺疾病的预防和治疗至关重要。
(中日友好医院呼吸与危重症医学科 沈焜路 摘译 林江涛 审校)
(Arch Gerontol Geriatr. 2024 Mar. DOI: 10.1016/j.archger.2023.105310)
(Arch Gerontol Geriatr. 2024 Mar. DOI: 10.1016/j.archger.2023.105310)
Causal relationship between frailty and chronic obstructive pulmonary disease or asthma: A two sample bidirectional Mendelian randomization study
Qu J, Liang Y, Rao Y, Pei Y, Li D, Zhang Y, Chen Y, Sun Y
Abstract
Background:Observational studies have established a strong association between frailty and obstructive lung diseases. However, the causal nature of this association remains unclear. To address this gap, we conducted a bidirectional Mendelian randomization (MR) study to investigate the causal relationship between frailty, as measured by the frailty index (FI), and chronic obstructive pulmonary disease (COPD) or asthma.
Methods:The latest meta-analysis of genome-wide association studies for FI, which included individuals of European ancestry from UK Biobank and TwinGene (N = 175,226), yielded the genetic instruments for frailty and outcome summary statistics. The genetic instrument for COPD and asthma, as well as the outcome summary data, were derived from the GWAS conducted on individuals of European ancestry from the FinnGen, with a sample size of 16,410 cases and 283,589 controls for COPD, and 37,253 cases and 187,112 controls for asthma. The analysis of MR was conducted employing the inverse-variance weighted (IVW) method, complemented by the weighted median method, MR-Egger regression, and MR pleiotropy residual sum and outlier (MR-PRESSO) test.
Results:Our results showed that genetically predicted higher FI was significantly associated with increased risk of COPD (odds ratio [OR] 1.75, 95 % confidence interval [CI] 1.29-2.36) and asthma (OR 2.10, 95 % CI 1.44-3.16). In the reverse direction analysis, genetic liability to both COPD (beta 0.06, 95 % CI 0.01-0.10) and asthma (beta 0.08, 95 % CI 0.06-0.11) showed significant associations with a higher FI.
Conclusion:Our research has reinforced the existing evidence supporting a reciprocal causal relationship between frailty and obstructive lung diseases. A deeper comprehension of this interconnection is imperative for the prevention and treatment of obstructive lung diseases.
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