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METABOLIC DISORDERS / BASIC RESEARCH
Lung function and nonalcoholic fatty liver disease: a Mendelian randomization study
1
Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Anhui Medical University, Hefei, China
2
Department of Infectious Disease, Hefei Second People’s Hospital, Hefei, China
3
Department of Occupational Disease, Hefei Third Clinical College of Anhui Medical University, Hefei, China
4
Department of Oncology, the First Affiliated Hospital of Anhui Medical University, Hefei, China
Submission date: 2023-03-06
Final revision date: 2023-06-18
Acceptance date: 2023-06-18
Online publication date: 2023-06-27
Publication date: 2025-02-28
Corresponding author
Ran Wang
Department of Respiratory and Critical Care Medicine The First Affiliated Hospital of Anhui Medical University Hefei 230022, China Phone: 86-551-62922913 Fax: 86-551-62922913
Department of Respiratory and Critical Care Medicine The First Affiliated Hospital of Anhui Medical University Hefei 230022, China Phone: 86-551-62922913 Fax: 86-551-62922913
Arch Med Sci 2025;21(1):197-205
KEYWORDS
forced expiratory volume in 1 s (FEV1)forced vital capacity (FVC)Mendelian randomizationnonalcoholic fatty liver diseaselung function
TOPICS
ABSTRACT
Introduction:
Associations of pulmonary function as evaluated by forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) with non-alcoholic fatty liver disease (NAFLD) have been reported in observational studies. Nevertheless, observational studies are susceptible to bias and reverse causality, making it difficult to infer the existence and direction of causality. We aimed to evaluate the causal effect of pulmonary function on NAFLD using the Mendelian randomization (MR) method.
Material and methods:
We performed univariate MR, multivariate MR, and bidirectional two-sample MR analyses to jointly assess the causal relationship between pulmonary function and NAFLD. In addition to the inverse variance weighting method as the primary MR analysis, three complementary methods were also performed. A series of sensitivity analyses were carried out to rule out pleiotropy.
Results:
We found that each genetically predicted (standard deviation) SD increase in FEV1 and FVC was associated with decreased NAFLD risk. However, after adjusting for height in the multivariate MR, only the effect of FEV1 on NAFLD risk remained significant. Furthermore, we found no causal effect of NAFLD on lung function in the reverse MR analysis.
Conclusions:
Our findings indicated that reduced lung function, especially FEV1, is causally associated with the risk of NAFLD. Although the mechanism remains unclear, FEV1 could be considered when assessing NAFLD risk and as a potential target for NAFLD prevention.
Associations of pulmonary function as evaluated by forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) with non-alcoholic fatty liver disease (NAFLD) have been reported in observational studies. Nevertheless, observational studies are susceptible to bias and reverse causality, making it difficult to infer the existence and direction of causality. We aimed to evaluate the causal effect of pulmonary function on NAFLD using the Mendelian randomization (MR) method.
Material and methods:
We performed univariate MR, multivariate MR, and bidirectional two-sample MR analyses to jointly assess the causal relationship between pulmonary function and NAFLD. In addition to the inverse variance weighting method as the primary MR analysis, three complementary methods were also performed. A series of sensitivity analyses were carried out to rule out pleiotropy.
Results:
We found that each genetically predicted (standard deviation) SD increase in FEV1 and FVC was associated with decreased NAFLD risk. However, after adjusting for height in the multivariate MR, only the effect of FEV1 on NAFLD risk remained significant. Furthermore, we found no causal effect of NAFLD on lung function in the reverse MR analysis.
Conclusions:
Our findings indicated that reduced lung function, especially FEV1, is causally associated with the risk of NAFLD. Although the mechanism remains unclear, FEV1 could be considered when assessing NAFLD risk and as a potential target for NAFLD prevention.
REFERENCES (37)
1.
Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology (Baltimore, Md) 2012; 55: 2005-23.
2.
Manne V, Handa P, Kowdley KV. Pathophysiology of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Clin Liver Dis 2018; 22: 23-37.
3.
Perumpail BJ, Khan MA, Yoo ER, Cholankeril G, Kim D, Ahmed A. Clinical epidemiology and disease burden of nonalcoholic fatty liver disease. World J Gastroenterol 2017; 23: 8263-76.
4.
Alqahtani SA, Chan WK, Yu ML. Hepatic outcomes of nonalcoholic fatty liver disease including cirrhosis and hepatocellular carcinoma. Clin Liver Dis 2023; 27: 211-23.
5.
Ziolkowska S, Binienda A, Jabłkowski M, Szemraj J, Czarny P. The interplay between insulin resistance, inflammation, oxidative stress, base excision repair and metabolic syndrome in nonalcoholic fatty liver disease. Int J Mol Sci 2021; 22: 11128.
6.
Fiorentino TV, Miceli S, Succurro E, Sciacqua A, Andreozzi F, Sesti G. Nonalcoholic fatty liver disease is associated with a decreased myocardial mechano-energetic efficiency. J Intern Med 2021; 289: 221-31.
7.
Han E, Lee YH, Kim YD, et al. Nonalcoholic fatty liver disease and sarcopenia are Independently associated with cardiovascular risk. Am J Gastroenterol 2020; 115: 584-95.
8.
Peng TC, Wu LW, Chen WL, Liaw FY, Chang YW, Kao TW. Nonalcoholic fatty liver disease and sarcopenia in a Western population (NHANES III): the importance of sarcopenia definition. Clin Nutr 2019; 38: 422-8.
9.
Mantovani A, Zaza G, Byrne CD, et al. Nonalcoholic fatty liver disease increases risk of incident chronic kidney disease: a systematic review and meta-analysis. Metabolism 2018; 79: 64-76.
10.
Yu Q, Lee YY, Xia ZY, Liong EC, Xiao J, Tipoe GL. S-allylmercaptocysteine improves nonalcoholic steatohepatitis by enhancing AHR/NRF2-mediated drug metabolising enzymes and reducing NF-B/IB and NLRP3/6-mediated inflammation. Eur J Nutr 2021; 60: 961-73.
11.
Cantero I, Abete I, Bullón-Vela V, et al. Fibroblast growth factor 21 levels and liver inflammatory biomarkers in obese subjects after weight loss. Arch Med Sci 2022; 18: 36-44.
12.
Małujło-Balcerska E, Sipowicz K, Pietras T. Comparing chronic obstructive pulmonary disease and depressive disorder in terms of inflammation-related biomarkers. Arch Med Sci 2023; 19: 814-9.
13.
Piccioni P, Tassinari R, Carosso A, Carena C, Bugiani M, Bono R. Lung function changes from childhood to adolescence: a seven-year follow-up study. BMC Pulm Med 2015; 15: 31.
14.
Zappala CJ, Latsi PI, Nicholson AG, et al. Marginal decline in forced vital capacity is associated with a poor outcome in idiopathic pulmonary fibrosis. Eur Respir J 2010; 35: 830-6.
15.
Soler Artigas M, Wain LV, Miller S, et al. Sixteen new lung function signals identified through 1000 Genomes Project reference panel imputation. Nat Commun 2015; 6: 8658.
16.
Ortega VE, Kumar R. The effect of ancestry and genetic variation on lung function predictions: what is “normal” lung function in diverse human populations? Curr Allergy Asthma Rep 2015; 15: 16.
17.
Cheng Y, Chen Q, Huang R, Lao C, Fu W. Moxibustion treatment increases the survival rate of lung infection of patients bed-ridden due to osteoporotic fracture of the spine via regulation of the inflammatory responses. Arch Med Sci 2023; 19: 258-63.
18.
Lee YY, Tsao YC, Yang CK, et al. Association between risk factors of metabolic syndrome with lung function. Eur J Clin Nutr 2020; 74: 811-7.
19.
Nerpin E, Jacinto T, Fonseca JA, Alving K, Janson C, Malinovschi A. Systemic inflammatory markers in relation to lung function in NHANES. 2007-2010. Respir Med 2018; 142: 94-100.
20.
Qin L, Zhang W, Yang Z, et al. Impaired lung function is associated with non-alcoholic fatty liver disease independently of metabolic syndrome features in middle-aged and elderly Chinese. BMC Endocr Disord 2017; 17: 18.
21.
Jung DH, Shim JY, Lee HR, Moon BS, Park BJ, Lee YJ. Relationship between non-alcoholic fatty liver disease and pulmonary function. Intern Med J 2012; 42: 541-6.
22.
Peng TC, Kao TW, Wu LW, et al. Association between pulmonary function and nonalcoholic fatty liver disease in the NHANES III study. Medicine 2015; 94: e907.
23.
Zhang Y, Liu Z, Choudhury T, Cornelis MC, Liu W. Habitual coffee intake and risk for nonalcoholic fatty liver disease: a two-sample Mendelian randomization study. Eur J Nutr 2021; 60: 1761-7.
24.
Burgess S, Scott RA, Timpson NJ, Davey Smith G, Thompson SG. Using published data in Mendelian randomization: a blueprint for efficient identification of causal risk factors. Eur J Epidemiol 2015; 30: 543-52.
25.
Lawlor DA, Harbord RM, Sterne JA, Timpson N, Davey Smith G. Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Stat Med 2008; 27: 1133-63.
26.
Burgess S, Butterworth A, Thompson SG. Mendelian randomization analysis with multiple genetic variants using summarized data. Genet Epidemiol 2013; 37: 658-65.
27.
Chen Y, Shen J, Wu Y, et al. Tea consumption and risk of lower respiratory tract infections: a two-sample mendelian randomization study. Eur J Nutr 2023; 62: 385-93.
28.
Bowden J, Davey Smith G, Burgess S. Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int J Epidemiol 2015; 44: 512-25.
29.
Burgess S, Bowden J, Fall T, Ingelsson E, Thompson SG. Sensitivity analyses for robust causal inference from mendelian randomization analyses with multiple genetic variants. Epidemiology 2017; 28: 30-42.
30.
Hartwig FP, Davey Smith G, Bowden J. Robust inference in summary data Mendelian randomization via the zero modal pleiotropy assumption. Int J Epidemiol 2017; 46: 1985-98.
31.
Au Yeung SL, Borges MC, Lawlor DA, Schooling CM. Impact of lung function on cardiovascular diseases and cardiovascular risk factors: a two sample bidirectional Mendelian randomisation study. Thorax 2022; 77: 164-71.
32.
VanDevanter DR, Pasta DJ. Evidence of diminished FEV1 and FVC in 6-year-olds followed in the European Cystic Fibrosis Patient Registry, 2007-2009. J Cyst Fibros 2013; 12: 786-9.
33.
Song JU, Jang Y, Lim SY, et al. Decreased lung function is associated with risk of developing non-alcoholic fatty liver disease: a longitudinal cohort study. PLoS One 2019; 14: e0208736.
34.
Miao L, Yang L, Guo LS, et al. Metabolic dysfunction-associated fatty liver disease is associated with greater impairment of lung function than nonalcoholic fatty liver disease. J Clin Transl Hepatol 2022; 10: 230-7.
35.
Miele CH, Grigsby MR, Siddharthan T, et al. Environmental exposures and systemic hypertension are risk factors for decline in lung function. Thorax 2018; 73: 1120-7.
36.
van Eeden SF, Tan WC, Suwa T, et al. Cytokines involved in the systemic inflammatory response induced by exposure to particulate matter air pollutants (PM(10)). Am J Respir Crit Care Med 2001; 164: 826-30.
37.
Luci C, Bourinet M, Leclère PS, Anty R, Gual P. Chronic inflammation in non-alcoholic steatohepatitis: molecular mechanisms and therapeutic strategies. Front Endocrinol 2020; 11: 597648.
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| ISSN: | 1734-1922 |
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