Alcohol intake and risk of rheumatoid arthritis: a Mendelian randomization study

Alkoholkonsum und Risiko der rheumatoiden Arthritis: eine Mendel-Randomisierungsstudie

Abstract

Objective

To examine whether alcohol intake is causally associated with rheumatoid arthritis (RA).

Methods

We performed a two-sample Mendelian randomization (MR) analysis using the inverse-variance weighted (IVW), weighted median, and MR-Egger regression methods. We used the publicly available summary statistics of alcohol intake frequency from the UK Biobank genome-wide association studies (GWASs; n = 336,965) as the exposure and a GWAS meta-analysis of 5539 autoantibody-positive RA patients and 20,169 controls as the outcome.

Results

We selected 24 single nucleotide polymorphisms (SNPs) associated with alcohol intake frequency at genome-wide significance as instrumental variables (IVs) to improve inference, 16 of which were inversely associated with RA. The IVW method showed no evidence of a causal association between alcohol intake and RA (beta = 0.218, SE = 0.213, p = 0.306). The MR-Egger regression revealed that directional pleiotropy was unlikely to bias the result (intercept = 0.027, p = 0.292). The MR-Egger analysis and the weighted median approach showed no causal association between alcohol intake and RA (beta = −0.778, SE = 0.947, p = 0.420 and beta = −0.286, SE = 0.302, p = 0.344, respectively). Cochran’s Q test did not indicate heterogeneity between IV estimates based on the individual variants, and results from a “leave-one-out” analysis demonstrated that no single SNP was driving the IVW point estimate.

Conclusion

The MR analysis does not support a causal inverse association between alcohol intake and RA occurrence.

Zusammenfassung

Ziel

In der vorliegenden Studie wurde untersucht, ob Alkoholkonsum kausal mit der rheumatoiden Arthritis (RA) zusammenhängt.

Methoden

Es wurde eine Zwei-Stichproben-Mendel-Randomisierungs(MR)-Analyse mit Inverse-Varianz-Gewichtung (IVG), gewichtetem Median und MR-Egger-Regression durchgeführt. Dafür herangezogen wurden die öffentlich zugänglichen statistischen Kennzahlen zur Häufigkeit des Alkoholkonsums aus den genomweiten Assoziationsstudien (GWAS) der UK Biobank (n = 336.965) für die Exposition sowie eine GWAS-Metaanalyse von 5539 Autoantikörper-positiven Patienten mit RA und 20.169 Kontrollpersonen für das Outcome.

Ergebnisse

Insgesamt 24 Einzelnukleotidpolymorphismen (SNP), die mit genomweiter Signifikanz mit der Häufigkeit des Alkoholkonsums assoziiert waren, wurden als Instrumentvariablen (IV) ausgewählt, um bessere Schlussfolgerungen zu ermöglichen. Von diesen waren 16 invers mit RA assoziiert. Die IVG-Methode ergab keinen Hinweis auf einen kausalen Zusammenhang zwischen Alkoholkonsum und RA (beta = 0,218, SE = 0,213, p = 0,306). Die MR-Egger-Regression zeigte, dass eine Verzerrung des Ergebnisses durch eine gerichtete Pleiotropie unwahrscheinlich war (Achsenabschnitt =0,027, p = 0,292). Die MR-Egger-Analyse und der Ansatz mit gewichtetem Median ergaben keinen kausalen Zusammenhang zwischen Alkoholkonsum und RA (beta = −0,778, SE = 0,947, p = 0,420 bzw. beta = −0,286, SE = 0,302, p = 0,344). Der Cochran-Q-Test wies nicht auf eine Heterogenität zwischen IV-Schätzungen auf Grundlage der individuellen Varianten hin, und eine Leave-one-out-Analyse zeigte, dass nicht ein einzelner SNP die IVG-Punktschätzung bestimmte.

Schlussfolgerung

Die MR-Analyse stützt eine kausale inverse Assoziation zwischen Alkoholkonsum und dem Auftreten einer RA nicht.

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Acknowledgements

This study was supported in part by a grant from the Korea Healthcare Technology R&D Project, Ministry for Health and Welfare, Republic of Korea (HI15C2958).

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Corresponding author

Correspondence to Y. H. Lee MD, PhD.

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Conflict of interest

S.-C. Bae and Y. H. Lee declare that they have no competing interests.

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1975 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

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U. Müller-Ladner, Bad Nauheim

U. Lange, Bad Nauheim

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Bae, S., Lee, Y.H. Alcohol intake and risk of rheumatoid arthritis: a Mendelian randomization study. Z Rheumatol 78, 791–796 (2019). https://doi.org/10.1007/s00393-018-0537-z

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Keywords

  • Alcohol intake
  • Rheumatoid arthritis
  • Mendelian randomization
  • Genetic predisposition to disease
  • Genome-wide association study

Schlüsselwörter

  • Alkoholkonsum
  • Rheumatoide Arthritis
  • Mendel-Randomisierung
  • Genetische Krankheitsdisposition
  • Genomweite Assoziationsstudie