The causal impact of smoking behavior on osteoarthritis: a Mendelian randomization analysis

ObjectiveAlthough smoking and osteoarthritis (OA) have been linked in a number of studies, the exact cause of the association is still unknown and the conclusion is controversial. The purpose of this study was to use Mendelian randomization (MR) analysis to investigate the causal relationship betwee...

Full description

Saved in:
Bibliographic Details
Main Authors: Qiang Xiao, Susu Dong, Yafen Tan, Xuan Zhang, Lu Yao, Qiuping Li, Tianli Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Public Health
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fpubh.2025.1437443/full
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832590880293257216
author Qiang Xiao
Susu Dong
Yafen Tan
Xuan Zhang
Lu Yao
Qiuping Li
Tianli Wang
author_facet Qiang Xiao
Susu Dong
Yafen Tan
Xuan Zhang
Lu Yao
Qiuping Li
Tianli Wang
author_sort Qiang Xiao
collection DOAJ
description ObjectiveAlthough smoking and osteoarthritis (OA) have been linked in a number of studies, the exact cause of the association is still unknown and the conclusion is controversial. The purpose of this study was to use Mendelian randomization (MR) analysis to investigate the causal relationship between smoking phenotypes and OA risk from a genetically informed standpoint.MethodsAs instrumental variables (IVs) based on single nucleotide polymorphisms (SNPs), this study used the summary-level data of corresponding genome-wide association study (GWAS) for five smoking phenotypes involving 1,694,781 samples. The outcomes comprised both a discovery and a replication cohort. The discovery MR analysis involved 12 OA traits (177,517 cases and 649,173 controls) while the replication MR analysis incorporated an additional OA GWAS dataset consisting of 36,185 cases and 135,185 controls. The main analytic approach we used was the inverse variance weighted (IVW) method. MR Egger, Weighted median, Weighted mode, and Simple mode were among the other methods that were tested. We conducted meta-analysis to combine the MR results. To confirm the robustness of the results, sensitivity analysis using Leave-One-Out (LOO), level pleiotropy testing (MR Egger intercept test and MR-PRESSO), and heterogeneity testing were performed.ResultsSummary-level MR analysis revealed a positive correlation between genetic predisposition for smoking and the likelihood of developing OA. The meta-analysis merge showed that smoking initiation increased the risk of knee OA by 20%, hip OA by 16%, and knee/hip OA by 19% (all p < 0.001). Similarly, lifetime smoking elevated the risk of knee OA by 101%, hip OA by 55%, and knee/hip OA by 84% (all p < 0.001). The sensitivity analysis’s findings reinforced the reliability of these findings.ConclusionAccording to our research, smoking increases the likelihood of developing OA from a genetic standpoint. Reducing tobacco use could, therefore, be beneficial in lowering the incidence of OA.
format Article
id doaj-art-51897caa41264cc5b9f42891a3a67304
institution Kabale University
issn 2296-2565
language English
publishDate 2025-01-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Public Health
spelling doaj-art-51897caa41264cc5b9f42891a3a673042025-01-23T06:55:59ZengFrontiers Media S.A.Frontiers in Public Health2296-25652025-01-011310.3389/fpubh.2025.14374431437443The causal impact of smoking behavior on osteoarthritis: a Mendelian randomization analysisQiang XiaoSusu DongYafen TanXuan ZhangLu YaoQiuping LiTianli WangObjectiveAlthough smoking and osteoarthritis (OA) have been linked in a number of studies, the exact cause of the association is still unknown and the conclusion is controversial. The purpose of this study was to use Mendelian randomization (MR) analysis to investigate the causal relationship between smoking phenotypes and OA risk from a genetically informed standpoint.MethodsAs instrumental variables (IVs) based on single nucleotide polymorphisms (SNPs), this study used the summary-level data of corresponding genome-wide association study (GWAS) for five smoking phenotypes involving 1,694,781 samples. The outcomes comprised both a discovery and a replication cohort. The discovery MR analysis involved 12 OA traits (177,517 cases and 649,173 controls) while the replication MR analysis incorporated an additional OA GWAS dataset consisting of 36,185 cases and 135,185 controls. The main analytic approach we used was the inverse variance weighted (IVW) method. MR Egger, Weighted median, Weighted mode, and Simple mode were among the other methods that were tested. We conducted meta-analysis to combine the MR results. To confirm the robustness of the results, sensitivity analysis using Leave-One-Out (LOO), level pleiotropy testing (MR Egger intercept test and MR-PRESSO), and heterogeneity testing were performed.ResultsSummary-level MR analysis revealed a positive correlation between genetic predisposition for smoking and the likelihood of developing OA. The meta-analysis merge showed that smoking initiation increased the risk of knee OA by 20%, hip OA by 16%, and knee/hip OA by 19% (all p < 0.001). Similarly, lifetime smoking elevated the risk of knee OA by 101%, hip OA by 55%, and knee/hip OA by 84% (all p < 0.001). The sensitivity analysis’s findings reinforced the reliability of these findings.ConclusionAccording to our research, smoking increases the likelihood of developing OA from a genetic standpoint. Reducing tobacco use could, therefore, be beneficial in lowering the incidence of OA.https://www.frontiersin.org/articles/10.3389/fpubh.2025.1437443/fullgenetic associationMendelian randomizationmeta-analysisosteoarthritissmoking
spellingShingle Qiang Xiao
Susu Dong
Yafen Tan
Xuan Zhang
Lu Yao
Qiuping Li
Tianli Wang
The causal impact of smoking behavior on osteoarthritis: a Mendelian randomization analysis
Frontiers in Public Health
genetic association
Mendelian randomization
meta-analysis
osteoarthritis
smoking
title The causal impact of smoking behavior on osteoarthritis: a Mendelian randomization analysis
title_full The causal impact of smoking behavior on osteoarthritis: a Mendelian randomization analysis
title_fullStr The causal impact of smoking behavior on osteoarthritis: a Mendelian randomization analysis
title_full_unstemmed The causal impact of smoking behavior on osteoarthritis: a Mendelian randomization analysis
title_short The causal impact of smoking behavior on osteoarthritis: a Mendelian randomization analysis
title_sort causal impact of smoking behavior on osteoarthritis a mendelian randomization analysis
topic genetic association
Mendelian randomization
meta-analysis
osteoarthritis
smoking
url https://www.frontiersin.org/articles/10.3389/fpubh.2025.1437443/full
work_keys_str_mv AT qiangxiao thecausalimpactofsmokingbehavioronosteoarthritisamendelianrandomizationanalysis
AT susudong thecausalimpactofsmokingbehavioronosteoarthritisamendelianrandomizationanalysis
AT yafentan thecausalimpactofsmokingbehavioronosteoarthritisamendelianrandomizationanalysis
AT xuanzhang thecausalimpactofsmokingbehavioronosteoarthritisamendelianrandomizationanalysis
AT luyao thecausalimpactofsmokingbehavioronosteoarthritisamendelianrandomizationanalysis
AT qiupingli thecausalimpactofsmokingbehavioronosteoarthritisamendelianrandomizationanalysis
AT tianliwang thecausalimpactofsmokingbehavioronosteoarthritisamendelianrandomizationanalysis
AT qiangxiao causalimpactofsmokingbehavioronosteoarthritisamendelianrandomizationanalysis
AT susudong causalimpactofsmokingbehavioronosteoarthritisamendelianrandomizationanalysis
AT yafentan causalimpactofsmokingbehavioronosteoarthritisamendelianrandomizationanalysis
AT xuanzhang causalimpactofsmokingbehavioronosteoarthritisamendelianrandomizationanalysis
AT luyao causalimpactofsmokingbehavioronosteoarthritisamendelianrandomizationanalysis
AT qiupingli causalimpactofsmokingbehavioronosteoarthritisamendelianrandomizationanalysis
AT tianliwang causalimpactofsmokingbehavioronosteoarthritisamendelianrandomizationanalysis