Causal relationship between asthma and gastroesophageal reflux disease based on two-sample Mendelian randomization_West China Medical Journal

Authors：

LIU Song ¹ ,  MA Jianling ² , SHI Liqing ² , LUO Jingshu ¹ , GUO Zhaodi ¹

1. The Second Clinical College of Beijing University of Chinese Medicine, Beijing 100029, P. R. China;
2. Respiratory Fever Department, Dongfang Hospital of Beijing University of Chinese Medicine, Beijing 100078, P. R. China;

Corresponding author：

MA Jianling, Email: ponymjl@sina.com

Keywords：

Asthma; gastroesophageal reflux disease; Mendelian randomization study; causal relationship

DOI：

10.7507/1002-0179.202311128

Video：

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Objective To evaluate the potential causal relationship between asthma and the risk of gastroesophageal reflux disease (GERD) using a two-sample Mendelian randomization study. Methods A large sample of genome-wide association study was used to summarize the data, and the genetic loci [single nucleotide polymorphisms (SNPs)] closely related to asthma were selected as instrumental variables, and Mendelian randomization analysis was conducted by inverse variance weighting, weighted median and MR-Egger method, respectively. At the same time, the multi-effect of MR-Egger was detected and the sensitivity analysis was carried out by Leave-one-out method to ensure the robustness of the results. Results A total of 77 SNPs closely related to asthma were selected as instrumental variables. The results of inverse variance weighted analysis showed a significant positive correlation between asthma and the occurrence of gastroesophageal reflux disease [odds ratio (OR)=1.044, 95% confidence interval (CI) (1.006, 1.083), P=0.024]. Weighted median results showed similar causality [OR=1.075, 95%CI (1.021, 1.133), P=0.006]. The MR-Egger regression results showed that there was a positive correlation between asthma and GERD, but there was no statistical significance [OR=1.080, 95%CI (0.983, 1.187), P=0.115]. The heterogeneity test results showed that there was no heterogeneity in the causal relationship between asthma and GERD (P>0.05). The results of the horizontal pleiotropy test showed that there was no horizontal pleiotropy in SNPs (P>0.05). The results of the retention test showed that no SNPs with significant impact on the results were detected. Conclusion There is a positive causal relationship between asthma and GERD.

Citation： LIU Song, MA Jianling, SHI Liqing, LUO Jingshu, GUO Zhaodi. Causal relationship between asthma and gastroesophageal reflux disease based on two-sample Mendelian randomization. West China Medical Journal, 2024, 39(4): 546-552. doi: 10.7507/1002-0179.202311128 Copy

1.	《中成药治疗优势病种临床应用指南》标准化项目组. 中成药治疗成人支气管哮喘临床应用指南(2021 年). 中国中西医结合杂志, 2022, 42(3): 276-286.
2.	Huang K, Yang T, Xu J, et al. Prevalence, risk factors, and management of asthma in China: a national cross-sectional study. Lancet, 2019, 394(10196): 407-418.
3.	中华医学会呼吸病学分会哮喘学组, 中国哮喘联盟. 重症哮喘诊断与处理中国专家共识. 中华结核和呼吸杂志, 2017, 40(11): 813-829.
4.	开赛尔·艾则孜, 古力巴哈尔·热孜克, 杨晓红. 胃食管反流与支气管哮喘之间的关系及抑酸药物对其的作用. 中华胃食管反流病电子杂志, 2019, 6(2): 70-74.
5.	Kiljander TO, Laitinen JO. The prevalence of gastroesophageal reflux disease in adult asthmatics. Chest, 2004, 126(5): 1490-1494.
6.	Debley JS, Carter ER, Redding GJ. Prevalence and impact of gastroesophageal reflux in adolescents with asthma: a population-based study. Pediatr Pulmonol, 2006, 41(5): 475-481.
7.	赵燕霞, 丛立, 开赛尔·艾则孜, 等. 支气管哮喘合并胃食管反流病相关危险因素分析. 中华胃食管反流病电子杂志, 2020, 7(3): 150-153.
8.	Sekula P, Del Greco MF, Pattaro C, et al. Mendelian randomization as an approach to assess causality using observational data. J Am Soc Nephrol, 2016, 27(11): 3253-3265.
9.	Davey Smith G, Hemani G. Mendelian randomization: genetic anchors for causal inference in epidemiological studies. Hum Mol Genet, 2014, 23(R1): R89-R98.
10.	Burgess S, Butterworth A, Thompson SG. Mendelian randomization analysis with multiple genetic variants using summarized data. Genet Epidemiol, 2013, 37(7): 658-665.
11.	Hemani G, Zheng J, Elsworth B, et al. The MR-base platform supports systematic causal inference across the human phenome. Elife, 2018, 7: e34408.
12.	Lee CH, Cook S, Lee JS, Han B. Comparison of two meta-analysis methods: inverse-variance-weighted average and weighted sum of z-scores. Genomics Inform, 2016, 14(4): 173-180.
13.	Ellingjord-Dale M, Papadimitriou N, Katsoulis M, et al. Coffee consumption and risk of breast cancer: a Mendelian randomization study. PLoS One, 2021, 16(1): e0236904.
14.	Huang S, Tian F, Yang X, et al. Physical activity and systemic lupus erythematosus among European populations: a two-sample Mendelian randomization study. Front Genet, 2022, 12: 784922.
15.	Burgess S, Thompson SG. Interpreting findings from Mendelian randomization using the MR-Egger method. Eur J Epidemiol, 2017, 32(5): 377-389.
16.	宁雅婵, 汪忠镐, 吴继敏, 等. 胃食管反流病 1014 例住院患者的诊治分析. 中华普外科手术学杂志(电子版), 2010, 4(3): 264-270.
17.	鲍永波, 姜向春, 元熙哲, 等. 胃食管反流和支气管哮喘的关系的研究. 中医临床研究, 2020, 12(16): 1-5.
18.	高翔, 刘殿刚, 张超, 等. 胃食管反流病与支气管哮喘关系研究进展. 中国医药, 2018, 13(3): 470-473.

1. 《中成药治疗优势病种临床应用指南》标准化项目组. 中成药治疗成人支气管哮喘临床应用指南(2021 年). 中国中西医结合杂志, 2022, 42(3): 276-286.
2. Huang K, Yang T, Xu J, et al. Prevalence, risk factors, and management of asthma in China: a national cross-sectional study. Lancet, 2019, 394(10196): 407-418.
3. 中华医学会呼吸病学分会哮喘学组, 中国哮喘联盟. 重症哮喘诊断与处理中国专家共识. 中华结核和呼吸杂志, 2017, 40(11): 813-829.
4. 开赛尔·艾则孜, 古力巴哈尔·热孜克, 杨晓红. 胃食管反流与支气管哮喘之间的关系及抑酸药物对其的作用. 中华胃食管反流病电子杂志, 2019, 6(2): 70-74.
5. Kiljander TO, Laitinen JO. The prevalence of gastroesophageal reflux disease in adult asthmatics. Chest, 2004, 126(5): 1490-1494.
6. Debley JS, Carter ER, Redding GJ. Prevalence and impact of gastroesophageal reflux in adolescents with asthma: a population-based study. Pediatr Pulmonol, 2006, 41(5): 475-481.
7. 赵燕霞, 丛立, 开赛尔·艾则孜, 等. 支气管哮喘合并胃食管反流病相关危险因素分析. 中华胃食管反流病电子杂志, 2020, 7(3): 150-153.
8. Sekula P, Del Greco MF, Pattaro C, et al. Mendelian randomization as an approach to assess causality using observational data. J Am Soc Nephrol, 2016, 27(11): 3253-3265.
9. Davey Smith G, Hemani G. Mendelian randomization: genetic anchors for causal inference in epidemiological studies. Hum Mol Genet, 2014, 23(R1): R89-R98.
10. Burgess S, Butterworth A, Thompson SG. Mendelian randomization analysis with multiple genetic variants using summarized data. Genet Epidemiol, 2013, 37(7): 658-665.
11. Hemani G, Zheng J, Elsworth B, et al. The MR-base platform supports systematic causal inference across the human phenome. Elife, 2018, 7: e34408.
12. Lee CH, Cook S, Lee JS, Han B. Comparison of two meta-analysis methods: inverse-variance-weighted average and weighted sum of z-scores. Genomics Inform, 2016, 14(4): 173-180.
13. Ellingjord-Dale M, Papadimitriou N, Katsoulis M, et al. Coffee consumption and risk of breast cancer: a Mendelian randomization study. PLoS One, 2021, 16(1): e0236904.
14. Huang S, Tian F, Yang X, et al. Physical activity and systemic lupus erythematosus among European populations: a two-sample Mendelian randomization study. Front Genet, 2022, 12: 784922.
15. Burgess S, Thompson SG. Interpreting findings from Mendelian randomization using the MR-Egger method. Eur J Epidemiol, 2017, 32(5): 377-389.
16. 宁雅婵, 汪忠镐, 吴继敏, 等. 胃食管反流病 1014 例住院患者的诊治分析. 中华普外科手术学杂志(电子版), 2010, 4(3): 264-270.
17. 鲍永波, 姜向春, 元熙哲, 等. 胃食管反流和支气管哮喘的关系的研究. 中医临床研究, 2020, 12(16): 1-5.
18. 高翔, 刘殿刚, 张超, 等. 胃食管反流病与支气管哮喘关系研究进展. 中国医药, 2018, 13(3): 470-473.

West China Medical Journal

Causal relationship between asthma and gastroesophageal reflux disease based on two-sample Mendelian randomization

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