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Smoking, alcohol consumption, and frailty: A Mendelian randomization study

Background: Tobacco smoking and alcohol consumption have been associated with frailty in observational studies. We sought to examine whether these associations reflect causality using the two-sample Mendelian randomization (MR) design. Methods: We used summary genome-wide association statistics for...

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Autores principales: Lv, Jiannan, Wu, Lianghua, Sun, Sheng, Yu, Huifang, Shen, Zekai, Xu, Jun, Zhu, Jiahao, Chen, Dingwan, Jiang, Minmin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9935614/
https://www.ncbi.nlm.nih.gov/pubmed/36816044
http://dx.doi.org/10.3389/fgene.2023.1092410
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author Lv, Jiannan
Wu, Lianghua
Sun, Sheng
Yu, Huifang
Shen, Zekai
Xu, Jun
Zhu, Jiahao
Chen, Dingwan
Jiang, Minmin
author_facet Lv, Jiannan
Wu, Lianghua
Sun, Sheng
Yu, Huifang
Shen, Zekai
Xu, Jun
Zhu, Jiahao
Chen, Dingwan
Jiang, Minmin
author_sort Lv, Jiannan
collection PubMed
description Background: Tobacco smoking and alcohol consumption have been associated with frailty in observational studies. We sought to examine whether these associations reflect causality using the two-sample Mendelian randomization (MR) design. Methods: We used summary genome-wide association statistics for smoking initiation (N = 2,669,029), alcohol consumption (N = 2,428,851), and the frailty index (FI, N = 175,226) in participants of European ancestry. Both univariable and multivariable MR were performed to comprehensively evaluate the independent effects of smoking and alcohol consumption on the FI, accompanied by multiple sensitivity analyses. Results were verified using lifetime smoking and alcohol use disorder. Reverse direction MR was undertaken to assess the potential for reverse causation. Results: Genetic predisposition to smoking initiation was significantly associated with increased FI (univariable MR: β = 0.345; 95% confidence interval [CI] = 0.316 to 0.374; p = 1.36E-113; multivariable MR: β = 0.219; 95% CI = 0.197 to 0.241; p = 2.44E-83). Genetically predicted alcohol consumption showed a suggestive association with the FI (univariable MR: β = −0.090; 95% CI = −0.151 to −0.029; p = 0.003; multivariable MR β = −0.153; 95% CI = −0.212 to −0.094; p = 2.03E-07), with inconsistent results in sensitivity analyses. In complementary analysis, genetic predicted lifetime smoking, but not alcohol use disorder was associated with the FI. There is no convincing evidence for reverse causation. Conclusion: The present MR study supported smoking as a causal risk factor of frailty. Further research is warranted to investigate whether alcohol consumption has a causal role in frailty.
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spelling pubmed-99356142023-02-18 Smoking, alcohol consumption, and frailty: A Mendelian randomization study Lv, Jiannan Wu, Lianghua Sun, Sheng Yu, Huifang Shen, Zekai Xu, Jun Zhu, Jiahao Chen, Dingwan Jiang, Minmin Front Genet Genetics Background: Tobacco smoking and alcohol consumption have been associated with frailty in observational studies. We sought to examine whether these associations reflect causality using the two-sample Mendelian randomization (MR) design. Methods: We used summary genome-wide association statistics for smoking initiation (N = 2,669,029), alcohol consumption (N = 2,428,851), and the frailty index (FI, N = 175,226) in participants of European ancestry. Both univariable and multivariable MR were performed to comprehensively evaluate the independent effects of smoking and alcohol consumption on the FI, accompanied by multiple sensitivity analyses. Results were verified using lifetime smoking and alcohol use disorder. Reverse direction MR was undertaken to assess the potential for reverse causation. Results: Genetic predisposition to smoking initiation was significantly associated with increased FI (univariable MR: β = 0.345; 95% confidence interval [CI] = 0.316 to 0.374; p = 1.36E-113; multivariable MR: β = 0.219; 95% CI = 0.197 to 0.241; p = 2.44E-83). Genetically predicted alcohol consumption showed a suggestive association with the FI (univariable MR: β = −0.090; 95% CI = −0.151 to −0.029; p = 0.003; multivariable MR β = −0.153; 95% CI = −0.212 to −0.094; p = 2.03E-07), with inconsistent results in sensitivity analyses. In complementary analysis, genetic predicted lifetime smoking, but not alcohol use disorder was associated with the FI. There is no convincing evidence for reverse causation. Conclusion: The present MR study supported smoking as a causal risk factor of frailty. Further research is warranted to investigate whether alcohol consumption has a causal role in frailty. Frontiers Media S.A. 2023-02-03 /pmc/articles/PMC9935614/ /pubmed/36816044 http://dx.doi.org/10.3389/fgene.2023.1092410 Text en Copyright © 2023 Lv, Wu, Sun, Yu, Shen, Xu, Zhu, Chen and Jiang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Lv, Jiannan
Wu, Lianghua
Sun, Sheng
Yu, Huifang
Shen, Zekai
Xu, Jun
Zhu, Jiahao
Chen, Dingwan
Jiang, Minmin
Smoking, alcohol consumption, and frailty: A Mendelian randomization study
title Smoking, alcohol consumption, and frailty: A Mendelian randomization study
title_full Smoking, alcohol consumption, and frailty: A Mendelian randomization study
title_fullStr Smoking, alcohol consumption, and frailty: A Mendelian randomization study
title_full_unstemmed Smoking, alcohol consumption, and frailty: A Mendelian randomization study
title_short Smoking, alcohol consumption, and frailty: A Mendelian randomization study
title_sort smoking, alcohol consumption, and frailty: a mendelian randomization study
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9935614/
https://www.ncbi.nlm.nih.gov/pubmed/36816044
http://dx.doi.org/10.3389/fgene.2023.1092410
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