Kausalzusammenhang zwischen Rauchen und dem verminderten Risiko für Arthrose: eine Mendel-Randomisierung

Translated title of the contribution: Causal association between smoking behavior and the decreased risk of osteoarthritis: a Mendelian randomization

Research output: Contribution to journalArticle

Abstract

Objective: This study aimed to examine whether smoking behavior is causally associated with osteoarthritis. Methods: A two-sample Mendelian randomization (MR) analysis using the inverse-variance weighted (IVW), weighted median, and MR-Egger regression methods was performed. We used the publicly available summary statistics datasets of smoking behavior genome-wide association studies (GWASs; n?= 85,997) as an exposure, and a GWAS in 7410 patients with osteoarthritis in the arcOGEN study and 11,009 controls of European ancestry as an outcome. Results: We selected four single nucleotide polymorphisms (SNPs) from GWASs of smoking behavior as instrumental variables (IVs) to improve inference. These SNPs were located at CHRNA3 (rs1051730), SLC25A5P5A9 (rs215614), CHRNB3 (rs6474412), and CYP2B6 (rs7260329). The IVW method showed evidence to support an inverse causal association between smoking behavior and osteoarthritis in the knee and hip (beta?= −0.056, standard error [SE]?= 0.027, p?= 0.035). MR-Egger regression revealed that directional pleiotropy was unlikely to be biasing the result (intercept?= −0.005; p?= 0.848), but showed no causal association between smoking behavior and osteoarthritis (beta?= −0.048, SE?= 0.048, p?= 0.427). However, the weighted median approach yielded evidence of a negative causal association between smoking behavior and osteoarthritis (beta?= −0.056, SE?= 0.028, p?= 0.046). Cochran’s Q test and the funnel plot indicated no evidence of heterogeneity between IV estimates based on the individual variants. Conclusion: The results of MR analysis support that smoking behavior was causally associated with a reduced risk of osteoarthritis.

Original languageGerman
Pages (from-to)1-6
Number of pages6
JournalZeitschrift fur Rheumatologie
DOIs
Publication statusAccepted/In press - 2018 Jul 5

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Random Allocation
Risk-Taking
Osteoarthritis
Smoking
Mendelian Randomization Analysis
Genome-Wide Association Study
Single Nucleotide Polymorphism
Hip Osteoarthritis
Knee Osteoarthritis

Keywords

  • Causal association
  • Mendelian randomization
  • Osteoarthritis
  • Smoking
  • Susceptibility

ASJC Scopus subject areas

  • Rheumatology

Cite this

@article{33a40f0b9d7b40be96f09956f959184f,
title = "Kausalzusammenhang zwischen Rauchen und dem verminderten Risiko f{\"u}r Arthrose: eine Mendel-Randomisierung",
abstract = "Objective: This study aimed to examine whether smoking behavior is causally associated with osteoarthritis. Methods: A two-sample Mendelian randomization (MR) analysis using the inverse-variance weighted (IVW), weighted median, and MR-Egger regression methods was performed. We used the publicly available summary statistics datasets of smoking behavior genome-wide association studies (GWASs; n?= 85,997) as an exposure, and a GWAS in 7410 patients with osteoarthritis in the arcOGEN study and 11,009 controls of European ancestry as an outcome. Results: We selected four single nucleotide polymorphisms (SNPs) from GWASs of smoking behavior as instrumental variables (IVs) to improve inference. These SNPs were located at CHRNA3 (rs1051730), SLC25A5P5A9 (rs215614), CHRNB3 (rs6474412), and CYP2B6 (rs7260329). The IVW method showed evidence to support an inverse causal association between smoking behavior and osteoarthritis in the knee and hip (beta?= −0.056, standard error [SE]?= 0.027, p?= 0.035). MR-Egger regression revealed that directional pleiotropy was unlikely to be biasing the result (intercept?= −0.005; p?= 0.848), but showed no causal association between smoking behavior and osteoarthritis (beta?= −0.048, SE?= 0.048, p?= 0.427). However, the weighted median approach yielded evidence of a negative causal association between smoking behavior and osteoarthritis (beta?= −0.056, SE?= 0.028, p?= 0.046). Cochran’s Q test and the funnel plot indicated no evidence of heterogeneity between IV estimates based on the individual variants. Conclusion: The results of MR analysis support that smoking behavior was causally associated with a reduced risk of osteoarthritis.",
keywords = "Causal association, Mendelian randomization, Osteoarthritis, Smoking, Susceptibility",
author = "Lee, {Young Ho}",
year = "2018",
month = "7",
day = "5",
doi = "10.1007/s00393-018-0505-7",
language = "German",
pages = "1--6",
journal = "Zeitschrift fur Rheumatologie",
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publisher = "D. Steinkopff-Verlag",

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TY - JOUR

T1 - Kausalzusammenhang zwischen Rauchen und dem verminderten Risiko für Arthrose

T2 - eine Mendel-Randomisierung

AU - Lee, Young Ho

PY - 2018/7/5

Y1 - 2018/7/5

N2 - Objective: This study aimed to examine whether smoking behavior is causally associated with osteoarthritis. Methods: A two-sample Mendelian randomization (MR) analysis using the inverse-variance weighted (IVW), weighted median, and MR-Egger regression methods was performed. We used the publicly available summary statistics datasets of smoking behavior genome-wide association studies (GWASs; n?= 85,997) as an exposure, and a GWAS in 7410 patients with osteoarthritis in the arcOGEN study and 11,009 controls of European ancestry as an outcome. Results: We selected four single nucleotide polymorphisms (SNPs) from GWASs of smoking behavior as instrumental variables (IVs) to improve inference. These SNPs were located at CHRNA3 (rs1051730), SLC25A5P5A9 (rs215614), CHRNB3 (rs6474412), and CYP2B6 (rs7260329). The IVW method showed evidence to support an inverse causal association between smoking behavior and osteoarthritis in the knee and hip (beta?= −0.056, standard error [SE]?= 0.027, p?= 0.035). MR-Egger regression revealed that directional pleiotropy was unlikely to be biasing the result (intercept?= −0.005; p?= 0.848), but showed no causal association between smoking behavior and osteoarthritis (beta?= −0.048, SE?= 0.048, p?= 0.427). However, the weighted median approach yielded evidence of a negative causal association between smoking behavior and osteoarthritis (beta?= −0.056, SE?= 0.028, p?= 0.046). Cochran’s Q test and the funnel plot indicated no evidence of heterogeneity between IV estimates based on the individual variants. Conclusion: The results of MR analysis support that smoking behavior was causally associated with a reduced risk of osteoarthritis.

AB - Objective: This study aimed to examine whether smoking behavior is causally associated with osteoarthritis. Methods: A two-sample Mendelian randomization (MR) analysis using the inverse-variance weighted (IVW), weighted median, and MR-Egger regression methods was performed. We used the publicly available summary statistics datasets of smoking behavior genome-wide association studies (GWASs; n?= 85,997) as an exposure, and a GWAS in 7410 patients with osteoarthritis in the arcOGEN study and 11,009 controls of European ancestry as an outcome. Results: We selected four single nucleotide polymorphisms (SNPs) from GWASs of smoking behavior as instrumental variables (IVs) to improve inference. These SNPs were located at CHRNA3 (rs1051730), SLC25A5P5A9 (rs215614), CHRNB3 (rs6474412), and CYP2B6 (rs7260329). The IVW method showed evidence to support an inverse causal association between smoking behavior and osteoarthritis in the knee and hip (beta?= −0.056, standard error [SE]?= 0.027, p?= 0.035). MR-Egger regression revealed that directional pleiotropy was unlikely to be biasing the result (intercept?= −0.005; p?= 0.848), but showed no causal association between smoking behavior and osteoarthritis (beta?= −0.048, SE?= 0.048, p?= 0.427). However, the weighted median approach yielded evidence of a negative causal association between smoking behavior and osteoarthritis (beta?= −0.056, SE?= 0.028, p?= 0.046). Cochran’s Q test and the funnel plot indicated no evidence of heterogeneity between IV estimates based on the individual variants. Conclusion: The results of MR analysis support that smoking behavior was causally associated with a reduced risk of osteoarthritis.

KW - Causal association

KW - Mendelian randomization

KW - Osteoarthritis

KW - Smoking

KW - Susceptibility

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