Physical Activity, Sedentary Behavior, and Osteoarthritis: A Two-Sample Mendelian Randomization Analysis
Abstract
Background: Sedentary behavior and physical activity are still ambiguous in their effects on osteoarthritis. We aimed to evaluate the effects of physical activity and sedentary behavior on osteoarthritis to provide a reference for the prevention of osteoarthritis.
Methods: This study was conducted in Changchun, China in 2022. We used two-sample Mendelian randomization with the SNP as an instrumental variable to investigate the effect of physical activity and sedentary behavior on osteoarthritis. In addition, a two-step Mendelian randomization method was used to test whether mediating factors (BMI, smoking, Apolipoprotein B) were involved in mediating the effects of exposure factors on osteoarthritis.
Results: TV watching was causally related to knee osteoarthritis and spine osteoarthritis, and they were positively correlated (knee osteoarthritis: OR=1.162,95 %CI: 1.027-1.315, P=0.017; spine osteoarthritis: OR=1.208,95 %CI: 1.033-1.413, P=0.018). BMI played a mediating role in the process of TV watching with knee osteoarthritis and spine osteoarthritis. ((The proportion of BMI mediating effect: knee osteoarthritis: 47.1% (95% CI: 36.7%~63.2%); spine osteoarthritis: 29.5% (95% CI: 19.3%~40.8%)). The proportion of Smoking mediating effect in the process of TV watching with spine osteoarthritis was 16.1% (95% CI: 3.7% ~ 31.6%).
Conclusion: TV watching is a potential risk factor for osteoarthritis and plays a role through modifiable factors such as BMI and smoking, therefore, interventions on these factors have the potential to reduce the burden of osteoarthritis caused by longer TV watching times.
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13. Davey Smith G, Ebrahim S, Lewis S, et al (2005).Genetic epidemiology and public health: hope, hype, and future prospects. Lancet, 366(9495):1484-98.
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16. Klimentidis YC, Raichlen DA, Bea J, et al (2018).Genome-wide association study of habitual physical activity in over 377,000 UK Biobank participants identifies multiple variants including CADM2 and APOE. Int J Obes (Lond), 42(6):1161-76.
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19. Boer CG, Hatzikotoulas K, Southam L, et al (2021).Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations. Cell, 184(18):4784-4818.
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21. Richardson TG, Sanderson E, Palmer TM, et al (2020).Evaluating the relationship between circulating lipoprotein lipids and apolipoproteins with risk of coronary heart disease: A multivariable Mendelian randomisation analysis. PLoS Med, 17(3):e1003062.
22. Bahls M, Leitzmann MF, Karch A, et al (2021).Physical activity, sedentary behavior and risk of coronary artery disease, myocardial infarction and ischemic stroke: a two-sample Mendelian randomization study. Clin Res Cardiol, 110(10):1564-73.
23. Kamat MA, Blackshaw JA, Young R, et al (2019).PhenoScanner V2: an expanded tool for searching human genotype-phenotype associations. Bioinformatics, 35(22):4851-3.
24. Brion MJ, Shakhbazov K, Visscher PM (2013).Calculating statistical power in Mendelian randomization studies. Int J Epidemiol, 42(5):1497-501.
25. Zhang J, Chen Z, Parna K, et al (2022).Mediators of the association between educational attainment and type 2 diabetes mellitus: a two-step multivariable Mendelian randomisation study. Diabetologia, 65(8):1364-74.
26. VanderWeele TJ (2016).Mediation Analysis: A Practitioner's Guide. Annu Rev Public Health, 37:17-32.
27. Burgess S, Daniel RM, Butterworth AS, et al (2015).Network Mendelian randomization: using genetic variants as instrumental variables to investigate mediation in causal pathways. Int J Epidemiol, 44(2):484-95.
28. Varbo A, Benn M, Smith GD, et al (2015).Remnant cholesterol, low-density lipoprotein cholesterol, and blood pressure as mediators from obesity to ischemic heart disease. Circ Res, 116(4):665-73.
29. Burgess S, Davey Smith G, Davies NM, et al (2023).Guidelines for performing Mendelian randomization investigations. Wellcome Open Res, 4:186.
30. Clark BK, Healy GN, Winkler EA, et al (2011).Relationship of television time with accelerometer-derived sedentary time: NHANES. Med Sci Sports Exerc, 43(5):822-8.
31. Lam TK, Moore SC, Brinton LA, et al (2013).Anthropometric measures and physical activity and the risk of lung cancer in never-smokers: a prospective cohort study. PLoS One, 8(8):e70672.
32. Gay C, Guiguet-Auclair C, Mourgues C, et al (2019).Physical activity level and association with behavioral factors in knee osteoarthritis. Ann Phys Rehabil Med, 62(1):14-20.
33. Ren Y, Hu J, Tan J, et al (2020).Incidence and risk factors of symptomatic knee osteoarthritis among the Chinese population: analysis from a nationwide longitudinal study. BMC Public Health, 20(1):1491.
34. Oiestad BE, Juhl CB, Culvenor AG, et al (2022).Knee extensor muscle weakness is a risk factor for the development of knee osteoarthritis: an updated systematic review and meta-analysis including 46 819 men and women. Br J Sports Med, 56(6):349-55.
35. Master H, Thoma LM, Dunlop DD, et al (2021).Joint Association of Moderate-to-vigorous Intensity Physical Activity and Sedentary Behavior With Incident Functional Limitation: Data From the Osteoarthritis Initiative. J Rheumatol, 48(9):1458-64.
36. Helajarvi H, Rosenstrom T, Pahkala K, et al (2014).Exploring causality between TV viewing and weight change in young and middle-aged adults. The Cardiovascular Risk in Young Finns study. PLoS One, 9(7):e101860.
37. Reyes C, Leyland KM, Peat G, et al (2016).Association Between Overweight and Obesity and Risk of Clinically Diagnosed Knee, Hip, and Hand Osteoarthritis: A Population-Based Cohort Study. Arthritis Rheumatol, 68(8):1869-75.
38. Climie RE, Grace MS, Larsen RL, et al (2018).Regular brief interruptions to sitting after a high-energy evening meal attenuate glycemic excursions in overweight/obese adults. Nutr Metab Cardiovasc Dis, 28(9):909-16.
39. Teichtahl AJ, Wang Y, Wluka AE, et al (2008).Obesity and knee osteoarthritis: new insights provided by body composition studies. Obesity (Silver Spring), 16(2):232-40.
40. Kong L, Wang L, Meng F, et al (2017). Association between smoking and risk of knee osteoarthritis: a systematic review and meta-analysis. Osteoarthritis Cartilage, 25(6):809-16.
41. Pearce F, Hui M, Ding C, et al (2013).Does smoking reduce the progression of osteoarthritis? Meta-analysis of observational studies. Arthritis Care Res (Hoboken), 65(7):1026-33.
42. Batty GD, Gale CR, Kivimaki M, et al (2020).Comparison of risk factor associations in UK Biobank against representative, general population based studies with conventional response rates: prospective cohort study and individual participant meta-analysis. BMJ, 368:m131.
2. Tang CH (2019).Research of Pathogenesis and Novel Therapeutics in Arthritis. Int J Mol Sci, 20(7):1646.
3. Nuesch E, Dieppe P, Reichenbach S, et al (2011).All cause and disease specific mortality in patients with knee or hip osteoarthritis: population based cohort study. BMJ, 342:d1165.
4. Braun J, Sieper J (2007).Ankylosing spondylitis. Lancet, 369(9570):1379-90.
5. Wang X, Perry TA, Arden N, et al (2020).Occupational Risk in Knee Osteoarthritis: A Systematic Review and Meta-Analysis of Observational Studies. Arthritis Care Res (Hoboken), 72(9):1213-23.
6. Reddigan JI, Ardern CI, Riddell MC, et al (2011).Relation of physical activity to cardiovascular disease mortality and the influence of cardiometabolic risk factors. Am J Cardiol, 108(10):1426-31.
7. Gay C, Chabaud A, Guilley E, et al (2016).Educating patients about the benefits of physical activity and exercise for their hip and knee osteoarthritis. Systematic literature review. Ann Phys Rehabil Med, 59(3):174-83.
8. Kanavaki AM, Rushton A, Efstathiou N, et al (2017).Barriers and facilitators of physical activity in knee and hip osteoarthritis: a systematic review of qualitative evidence. BMJ Open, 7(12):e017042.
9. Huang G, Cai J, Li W, et al (2023).A Mendelian randomization study on causal effects of leisure sedentary behaviour on the risk of rheumatoid arthritis. Eur J Clin Invest,53(3):e13894.
10. He Q, Bennett AN, Fan B, et al (2022).Assessment of Bidirectional Relationships between Leisure Sedentary Behaviors and Neuropsychiatric Disorders: A Two-Sample Mendelian Randomization Study. Genes (Basel), 13(6).
11. Gao Y, Mi J, Liu Z, et al (2021).Leisure Sedentary Behavior and Risk of Lung Cancer: A Two-Sample Mendelian Randomization Study and Mediation Analysis. Front Genet, 12:763626.
12. Berenbaum F, Wallace IJ, Lieberman DE, et al (2018).Modern-day environmental factors in the pathogenesis of osteoarthritis. Nat Rev Rheumatol, 14(11):674-81.
13. Davey Smith G, Ebrahim S, Lewis S, et al (2005).Genetic epidemiology and public health: hope, hype, and future prospects. Lancet, 366(9495):1484-98.
14. Lawlor DA, Harbord RM, Sterne JA, et al (2008).Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Stat Med, 27(8):1133-63.
15. To K, Romain K, Mak C, et al (2020).The Treatment of Cartilage Damage Using Human Mesenchymal Stem Cell-Derived Extracellular Vesicles: A Systematic Review of in vivo Studies. Front Bioeng Biotechnol, 8:580.
16. Klimentidis YC, Raichlen DA, Bea J, et al (2018).Genome-wide association study of habitual physical activity in over 377,000 UK Biobank participants identifies multiple variants including CADM2 and APOE. Int J Obes (Lond), 42(6):1161-76.
17. Doherty A, Jackson D, Hammerla N, et al (2017).Large Scale Population Assessment of Physical Activity Using Wrist Worn Accelerometers: The UK Biobank Study. PLoS One, 12(2):e0169649.
18. van de Vegte YJ, Said MA, Rienstra M, et al (2020).Genome-wide association studies and Mendelian randomization analyses for leisure sedentary behaviours. Nat Commun, 11(1):1770.
19. Boer CG, Hatzikotoulas K, Southam L, et al (2021).Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations. Cell, 184(18):4784-4818.
20. Liu M, Jiang Y, Wedow R, et al (2019).Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use. Nat Genet, 51(2):237-44.
21. Richardson TG, Sanderson E, Palmer TM, et al (2020).Evaluating the relationship between circulating lipoprotein lipids and apolipoproteins with risk of coronary heart disease: A multivariable Mendelian randomisation analysis. PLoS Med, 17(3):e1003062.
22. Bahls M, Leitzmann MF, Karch A, et al (2021).Physical activity, sedentary behavior and risk of coronary artery disease, myocardial infarction and ischemic stroke: a two-sample Mendelian randomization study. Clin Res Cardiol, 110(10):1564-73.
23. Kamat MA, Blackshaw JA, Young R, et al (2019).PhenoScanner V2: an expanded tool for searching human genotype-phenotype associations. Bioinformatics, 35(22):4851-3.
24. Brion MJ, Shakhbazov K, Visscher PM (2013).Calculating statistical power in Mendelian randomization studies. Int J Epidemiol, 42(5):1497-501.
25. Zhang J, Chen Z, Parna K, et al (2022).Mediators of the association between educational attainment and type 2 diabetes mellitus: a two-step multivariable Mendelian randomisation study. Diabetologia, 65(8):1364-74.
26. VanderWeele TJ (2016).Mediation Analysis: A Practitioner's Guide. Annu Rev Public Health, 37:17-32.
27. Burgess S, Daniel RM, Butterworth AS, et al (2015).Network Mendelian randomization: using genetic variants as instrumental variables to investigate mediation in causal pathways. Int J Epidemiol, 44(2):484-95.
28. Varbo A, Benn M, Smith GD, et al (2015).Remnant cholesterol, low-density lipoprotein cholesterol, and blood pressure as mediators from obesity to ischemic heart disease. Circ Res, 116(4):665-73.
29. Burgess S, Davey Smith G, Davies NM, et al (2023).Guidelines for performing Mendelian randomization investigations. Wellcome Open Res, 4:186.
30. Clark BK, Healy GN, Winkler EA, et al (2011).Relationship of television time with accelerometer-derived sedentary time: NHANES. Med Sci Sports Exerc, 43(5):822-8.
31. Lam TK, Moore SC, Brinton LA, et al (2013).Anthropometric measures and physical activity and the risk of lung cancer in never-smokers: a prospective cohort study. PLoS One, 8(8):e70672.
32. Gay C, Guiguet-Auclair C, Mourgues C, et al (2019).Physical activity level and association with behavioral factors in knee osteoarthritis. Ann Phys Rehabil Med, 62(1):14-20.
33. Ren Y, Hu J, Tan J, et al (2020).Incidence and risk factors of symptomatic knee osteoarthritis among the Chinese population: analysis from a nationwide longitudinal study. BMC Public Health, 20(1):1491.
34. Oiestad BE, Juhl CB, Culvenor AG, et al (2022).Knee extensor muscle weakness is a risk factor for the development of knee osteoarthritis: an updated systematic review and meta-analysis including 46 819 men and women. Br J Sports Med, 56(6):349-55.
35. Master H, Thoma LM, Dunlop DD, et al (2021).Joint Association of Moderate-to-vigorous Intensity Physical Activity and Sedentary Behavior With Incident Functional Limitation: Data From the Osteoarthritis Initiative. J Rheumatol, 48(9):1458-64.
36. Helajarvi H, Rosenstrom T, Pahkala K, et al (2014).Exploring causality between TV viewing and weight change in young and middle-aged adults. The Cardiovascular Risk in Young Finns study. PLoS One, 9(7):e101860.
37. Reyes C, Leyland KM, Peat G, et al (2016).Association Between Overweight and Obesity and Risk of Clinically Diagnosed Knee, Hip, and Hand Osteoarthritis: A Population-Based Cohort Study. Arthritis Rheumatol, 68(8):1869-75.
38. Climie RE, Grace MS, Larsen RL, et al (2018).Regular brief interruptions to sitting after a high-energy evening meal attenuate glycemic excursions in overweight/obese adults. Nutr Metab Cardiovasc Dis, 28(9):909-16.
39. Teichtahl AJ, Wang Y, Wluka AE, et al (2008).Obesity and knee osteoarthritis: new insights provided by body composition studies. Obesity (Silver Spring), 16(2):232-40.
40. Kong L, Wang L, Meng F, et al (2017). Association between smoking and risk of knee osteoarthritis: a systematic review and meta-analysis. Osteoarthritis Cartilage, 25(6):809-16.
41. Pearce F, Hui M, Ding C, et al (2013).Does smoking reduce the progression of osteoarthritis? Meta-analysis of observational studies. Arthritis Care Res (Hoboken), 65(7):1026-33.
42. Batty GD, Gale CR, Kivimaki M, et al (2020).Comparison of risk factor associations in UK Biobank against representative, general population based studies with conventional response rates: prospective cohort study and individual participant meta-analysis. BMJ, 368:m131.
| Files | ||
| Issue | Vol 52 No 10 (2023) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijph.v52i10.13848 | |
| Keywords | ||
| Osteoarthritis Sedentary behavior Mendelian randomization Lifestyle | ||
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How to Cite
1.
Wang Y, Zhang Y, Zhao C, Cai W, Wang Z, Zhao W. Physical Activity, Sedentary Behavior, and Osteoarthritis: A Two-Sample Mendelian Randomization Analysis. Iran J Public Health. 2023;52(10):2099-2108.
