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胃食管反流病与特发性肺纤维化之间的因果关系：双向双样本孟德尔随机研究
European Respiratory Journal
(
IF
16.6
)
Pub Date : 2023-05-25
, DOI:
10.1183/13993003.01585-2022
Carl J Reynolds
1
,
Fabiola Del Greco M
2
,
Richard J Allen
3,
4
,
Carlos Flores
5,
6,
7,
8
,
R Gisli Jenkins
9
,
Toby M Maher
9,
10
,
Philip L Molyneaux
9
,
Imre Noth
11
,
Justin M Oldham
12
,
Louise V Wain
3,
4
,
Jiyuan An
13
,
Jue-Sheng Ong
14
,
Stuart MacGregor
14
,
Tom A Yates
15
,
Paul Cullinan
9
,
Cosetta Minelli
9
Affiliation
- National Heart and Lung Institute, Imperial College London, London, UK
- Institute for Biomedicine, Eurac Research, Bolzano, Italy.
- Department of Population Health Sciences, University of Leicester, Leicester, UK.
- National Institute for Health Research, Leicester Respiratory Biomedical Research Centre, Glenfield Hospital, Leicester, UK.
- Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain.
- CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.
- Genomics Division, Instituto Tecnológico y de Energías Renovables, Santa Cruz de Tenerife, Spain.
- Faculty of Health Sciences, University of Fernando Pessoa Canarias, Las Palmas de Gran Canaria, Spain.
- National Heart and Lung Institute, Imperial College London, London, UK.
- Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
- Division of Pulmonary and Critical Care Medicine, University of Virginia, Charlottesville, VA, USA.
- Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA.
- Centre for Agriculture and the Bioeconomy, Faculty of Science, Queensland University of Technology, Brisbane, Australia.
- Population Health Department, QIMR Berghofer Medical Research Institute, Herston, Australia.
- Division of Infection and Immunity, Faculty of Medicine, University College London, London, UK.
背景
在观察性研究中，胃食管反流病（GORD）与特发性肺纤维化（IPF）相关。目前尚不清楚这种关联的产生是因为 GORD 导致 IPF，还是因为 IPF 导致 GORD，或者是因为与 GORD 和 IPF 相关的因素（例如吸烟）的混杂。我们使用双向孟德尔随机化 (MR)，其中遗传变异被用作工具变量来解决混杂和反向因果关系问题，以检查 GORD 和 IPF 是如何（如果有的话）因果关系的。
方法
使用最大的 GORD（78 707 例病例和 288 734 例对照）和 IPF（4125 例病例和 20 464 例对照）的遗传数据进行双向双样本 MR，以评估 GORD 对 IPF 风险和 IPF 对 GORD 风险的因果影响。 ）目前可用的全基因组关联荟萃分析。
结果
GORD 增加 IPF 风险，OR 为 1.6（95% CI 1.04–2.49；p=0.032）。没有证据表明 IPF 对 GORD 风险存在因果影响，OR 为 0.999（95% CI 0.997–1.000；p=0.245）。
结论
我们发现 GORD 会增加 IPF 的风险，但没有发现任何证据表明 IPF 会增加 GORD 的风险。在未来的 IPF 风险研究中应考虑 GORD，并应更新其作为潜在治疗靶点的兴趣。还应研究 GORD 对 IPF 影响的机制。
"点击查看英文标题和摘要"
The causal relationship between gastro-oesophageal reflux disease and idiopathic pulmonary fibrosis: a bidirectional two-sample Mendelian randomisation study
Background
Gastro-oesophageal reflux disease (GORD) is associated with idiopathic pulmonary fibrosis (IPF) in observational studies. It is not known if this association arises because GORD causes IPF or because IPF causes GORD, or because of confounding by factors, such as smoking, associated with both GORD and IPF. We used bidirectional Mendelian randomisation (MR), where genetic variants are used as instrumental variables to address issues of confounding and reverse causation, to examine how, if at all, GORD and IPF are causally related.
Methods
A bidirectional two-sample MR was performed to estimate the causal effect of GORD on IPF risk and of IPF on GORD risk, using genetic data from the largest GORD (78 707 cases and 288 734 controls) and IPF (4125 cases and 20 464 controls) genome-wide association meta-analyses currently available.
Results
GORD increased the risk of IPF, with an OR of 1.6 (95% CI 1.04–2.49; p=0.032). There was no evidence of a causal effect of IPF on the risk of GORD, with an OR of 0.999 (95% CI 0.997–1.000; p=0.245).
Conclusions
We found that GORD increases the risk of IPF, but found no evidence that IPF increases the risk of GORD. GORD should be considered in future studies of IPF risk and interest in it as a potential therapeutic target should be renewed. The mechanisms underlying the effect of GORD on IPF should also be investigated.
更新日期：2023-05-25
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