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

Originalien

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

Smoking Osteoarthritis Mendelian randomization Causal association Susceptibility 

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

Zusammenfassung

Ziel

Die vorliegenden Studie hatte das Ziel, zu untersuchen, ob Rauchen kausal mit Arthrose verknüpft ist.

Methoden

Dazu wurde die Analyse einer 2‑Stichproben-Mendel-Randomisierung (MR) unter Einsatz von Verfahren mit inverser Varianzgewichtung (IVW), gewichtetem Mittel und der MR-Egger-Regression durchgeführt. Die Autoren verwendeten die Metaanalysen der öffentlich zugänglichen zusammenfassenden statistischen Datensätze von genomweiten Assoziationsstudien (GWAS) zum Rauchverhalten (n = 85.997) als Exposition und eine GWAS zu 7410 Arthrosepatienten aus der arcOGEN-Studie sowie 11.009 Kontrollen europäischer Abstammung als Endpunkt.

Ergebnisse

Für die Ableitung gezielterer Schlussfolgerungen wurden 4 Einzelnukleotidpolymorphismen (SNPs) aus den GWAS zum Rauchverhalten als instrumentelle Variablen (IV) ausgewählt. Diese SNPs waren auf CHRNA3 (rs1051730), SLC25A5P5A9 (rs215614), CHRNB3 (rs6474412) und CYP2B6 (rs7260329) lokalisiert. Durch die IVW-Methode ergaben sich Hinweise, die einen inversen Kausalzusammenhang zwischen Rauchen und Arthrose im Knie und in der Hüfte stützen (β = −0,056; Standardfehler [„standard error“, SE]:  0,027; p = 0,035). Die MR-Egger-Regression zeigte, dass es unwahrscheinlich war, dass die direktionale Pleiotropie eine Quelle für Bias beim Ergebnis darstellte („intercept“ = −0,005; p = 0,848), aber sie ergab keinen Kausalzusammenhang zwischen Rauchen und Arthrose (β = −0,048; SE = 0,048; p = 0,427). Allerdings erbrachte der Ansatz unter Verwendung des gewichteten Mittels Hinweise auf einen negativen Kausalzusammenhang zwischen Rauchen und Arthrose (β = −0,056; SE = 0,028; p = 0,046). Der Q‑Test nach Cochran und der Funnel Plot ergaben keine Hinweise auf Heterogenität zwischen IV-Schätzwerten auf der Basis der individuellen Varianten.

Schlussfolgerung

Die Ergebnisse der MR-Analyse unterstützen die These, dass Rauchen kausal mit einem verminderten Risiko für Arthrose verknüpft sei.

Schlüsselwörter

Rauchen Arthrose Mendel-Randomisierung Kausalzusammenhang Anfälligkeit 

Notes

Compliance with ethical guidelines

Conflict of interest

Y.H. Lee declares that he has no competing interests.

This article does not contain any studies with human participants or animals performed by any of the authors.

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Copyright information

© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2018

Authors and Affiliations

  1. 1.Department of RheumatologyKorea University Anam Hospital, Korea University College of MedicineSeoulKorea (Republic of)

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