Univariable and Multivariable Two-Sample Mendelian Randomization Investigating the Effects of Leisure Sedentary Behaviors on the Risk of Lung Cancer
Background:Leisure sedentary behaviors (LSB) are widespread, and observational studies have provided emerging evidence that LSB play a role in the development of lung cancer (LC). However, the causal inference between LSB and LC remains unknown.Methods: We utilized univariable (UVMR) and multivariab...
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2021
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oai:doaj.org-article:d14e00471deb4cca8879614e0f6dd9992021-11-30T17:45:48ZUnivariable and Multivariable Two-Sample Mendelian Randomization Investigating the Effects of Leisure Sedentary Behaviors on the Risk of Lung Cancer1664-802110.3389/fgene.2021.742718https://doaj.org/article/d14e00471deb4cca8879614e0f6dd9992021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fgene.2021.742718/fullhttps://doaj.org/toc/1664-8021Background:Leisure sedentary behaviors (LSB) are widespread, and observational studies have provided emerging evidence that LSB play a role in the development of lung cancer (LC). However, the causal inference between LSB and LC remains unknown.Methods: We utilized univariable (UVMR) and multivariable two-sample Mendelian randomization (MVMR) analysis to disentangle the effects of LSB on the risk of LC. MR analysis was conducted with genetic variants from genome-wide association studies of LSB (408,815 persons from UK Biobank), containing 152 single-nucleotide polymorphisms (SNPs) for television (TV) watching, 37 SNPs for computer use, and four SNPs for driving, and LC from the International Lung Cancer Consortium (11,348 cases and 15,861 controls). Multiple sensitivity analyses were further performed to verify the causality.Results: UVMR demonstrated that genetically predisposed 1.5-h increase in LSB spent on watching TV increased the odds of LC by 90% [odds ratio (OR), 1.90; 95% confidence interval (CI), 1.44–2.50; p < 0.001]. Similar trends were observed for squamous cell lung cancer (OR, 1.97; 95%CI, 1.31–2.94; p = 0.0010) and lung adenocarcinoma (OR, 1.64; 95%CI 1.12–2.39; p = 0.0110). The causal effects remained significant after adjusting for education (OR, 1.97; 95%CI, 1.44–2.68; p < 0.001) and body mass index (OR, 1.86; 95%CI, 1.36–2.54; p < 0.001) through MVMR approach. No association was found between prolonged LSB spent on computer use and driving and LC risk. Genetically predisposed prolonged LSB was additionally correlated with smoking (OR, 1.557; 95%CI, 1.287–1.884; p < 0.001) and alcohol consumption (OR, 1.010; 95%CI, 1.004–1.016; p = 0.0016). Consistency of results across complementary sensitivity MR methods further strengthened the causality.Conclusion: Robust evidence was demonstrated for an independent, causal effect of LSB spent on watching TV in increasing the risk of LC. Further work is necessary to investigate the potential mechanisms.Haoxin PengHaoxin PengXiangrong WuXiangrong WuYaokai WenYaokai WenYiyuan AoYiyuan AoYutian LiWenhui GuanJinsheng LinCaichen LiHengrui LiangJianxing HeWenhua LiangWenhua LiangFrontiers Media S.A.articleleisure sedentary behaviorslung cancerMendelian randomizationcancer preventionsingle-neucleotide polymorphismGeneticsQH426-470ENFrontiers in Genetics, Vol 12 (2021) |
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leisure sedentary behaviors lung cancer Mendelian randomization cancer prevention single-neucleotide polymorphism Genetics QH426-470 |
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leisure sedentary behaviors lung cancer Mendelian randomization cancer prevention single-neucleotide polymorphism Genetics QH426-470 Haoxin Peng Haoxin Peng Xiangrong Wu Xiangrong Wu Yaokai Wen Yaokai Wen Yiyuan Ao Yiyuan Ao Yutian Li Wenhui Guan Jinsheng Lin Caichen Li Hengrui Liang Jianxing He Wenhua Liang Wenhua Liang Univariable and Multivariable Two-Sample Mendelian Randomization Investigating the Effects of Leisure Sedentary Behaviors on the Risk of Lung Cancer |
| description |
Background:Leisure sedentary behaviors (LSB) are widespread, and observational studies have provided emerging evidence that LSB play a role in the development of lung cancer (LC). However, the causal inference between LSB and LC remains unknown.Methods: We utilized univariable (UVMR) and multivariable two-sample Mendelian randomization (MVMR) analysis to disentangle the effects of LSB on the risk of LC. MR analysis was conducted with genetic variants from genome-wide association studies of LSB (408,815 persons from UK Biobank), containing 152 single-nucleotide polymorphisms (SNPs) for television (TV) watching, 37 SNPs for computer use, and four SNPs for driving, and LC from the International Lung Cancer Consortium (11,348 cases and 15,861 controls). Multiple sensitivity analyses were further performed to verify the causality.Results: UVMR demonstrated that genetically predisposed 1.5-h increase in LSB spent on watching TV increased the odds of LC by 90% [odds ratio (OR), 1.90; 95% confidence interval (CI), 1.44–2.50; p < 0.001]. Similar trends were observed for squamous cell lung cancer (OR, 1.97; 95%CI, 1.31–2.94; p = 0.0010) and lung adenocarcinoma (OR, 1.64; 95%CI 1.12–2.39; p = 0.0110). The causal effects remained significant after adjusting for education (OR, 1.97; 95%CI, 1.44–2.68; p < 0.001) and body mass index (OR, 1.86; 95%CI, 1.36–2.54; p < 0.001) through MVMR approach. No association was found between prolonged LSB spent on computer use and driving and LC risk. Genetically predisposed prolonged LSB was additionally correlated with smoking (OR, 1.557; 95%CI, 1.287–1.884; p < 0.001) and alcohol consumption (OR, 1.010; 95%CI, 1.004–1.016; p = 0.0016). Consistency of results across complementary sensitivity MR methods further strengthened the causality.Conclusion: Robust evidence was demonstrated for an independent, causal effect of LSB spent on watching TV in increasing the risk of LC. Further work is necessary to investigate the potential mechanisms. |
| format |
article |
| author |
Haoxin Peng Haoxin Peng Xiangrong Wu Xiangrong Wu Yaokai Wen Yaokai Wen Yiyuan Ao Yiyuan Ao Yutian Li Wenhui Guan Jinsheng Lin Caichen Li Hengrui Liang Jianxing He Wenhua Liang Wenhua Liang |
| author_facet |
Haoxin Peng Haoxin Peng Xiangrong Wu Xiangrong Wu Yaokai Wen Yaokai Wen Yiyuan Ao Yiyuan Ao Yutian Li Wenhui Guan Jinsheng Lin Caichen Li Hengrui Liang Jianxing He Wenhua Liang Wenhua Liang |
| author_sort |
Haoxin Peng |
| title |
Univariable and Multivariable Two-Sample Mendelian Randomization Investigating the Effects of Leisure Sedentary Behaviors on the Risk of Lung Cancer |
| title_short |
Univariable and Multivariable Two-Sample Mendelian Randomization Investigating the Effects of Leisure Sedentary Behaviors on the Risk of Lung Cancer |
| title_full |
Univariable and Multivariable Two-Sample Mendelian Randomization Investigating the Effects of Leisure Sedentary Behaviors on the Risk of Lung Cancer |
| title_fullStr |
Univariable and Multivariable Two-Sample Mendelian Randomization Investigating the Effects of Leisure Sedentary Behaviors on the Risk of Lung Cancer |
| title_full_unstemmed |
Univariable and Multivariable Two-Sample Mendelian Randomization Investigating the Effects of Leisure Sedentary Behaviors on the Risk of Lung Cancer |
| title_sort |
univariable and multivariable two-sample mendelian randomization investigating the effects of leisure sedentary behaviors on the risk of lung cancer |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/d14e00471deb4cca8879614e0f6dd999 |
| work_keys_str_mv |
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| _version_ |
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