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Investigating the possible causal association of coffee consumption with osteoarthritis risk using a Mendelian randomization analysis

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Abstract

This study examined whether coffee consumption is causally associated with osteoarthritis. A two-sample Mendelian randomization (MR) analysis using inverse-variance weighted (IVW) and weighted median estimates, and the MR-Egger regression method were performed. The publicly available summary statistical datasets of coffee consumption genome-wide association studies (GWASs) meta-analyses on coffee intake from eight Caucasian cohorts (n = 18,176), GWAS meta-analyses of predominately regular-type coffee consumers of European ancestry (n = up to 91,462), and a GWAS in 7410 patients with osteoarthritis in the arcOGEN study with 11,009 controls of European ancestry were evaluated. Four single-nucleotide polymorphisms (SNPs) from GWASs of coffee consumption as instrumental variables (IVs) to improve inference were selected. These SNPs were located at neurocalcin delta (NCALD) (rs16868941), cytochrome p450 oxidoreductase (POR) (rs17685), cytochrome p450 family 1 subfamily A member 1 (CYP1A1) (rs2470893), and neuronal cell adhesion molecule (NRCAM) (rs382140). The IVW method (beta = 0.381, SE = 0.170, p = 0.025) and the weighted median approach (beta = 0.419, SE = 0.206, p = 0.047) showed evidence to support a causal association between coffee consumption and osteoarthritis. MR-Egger regression revealed that directional pleiotropy was unlikely to be biasing the result (intercept = 0.064; p = 0.549), but showed no causal association between coffee consumption and osteoarthritis (beta = − 0.518, SE = 1.270, p = 0.723). Cochran’s Q test and the funnel plot indicated no evidence of heterogeneity between IV estimates based on the individual variants. The results of MR analysis support the observation that coffee consumption is causally associated with an increased risk of osteoarthritis.

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References

  1. Dieppe PA, Lohmander LS (2005) Pathogenesis and management of pain in osteoarthritis. Lancet 365:965–973

    Article  CAS  Google Scholar 

  2. Litwic A, Edwards MH, Dennison EM, Cooper C (2013) Epidemiology and burden of osteoarthritis. Br Med Bull 105:185–199

    Article  Google Scholar 

  3. Kim D, Cho S-K, Nam SW, Kwon HH, Jung S-Y, Jeon CH, Im SG, Kim D, Jang EJ, Sung Y-K (2017) Cardiovascular and gastrointestinal effects of Etoricoxib in the treatment of osteoarthritis: a systematic review and network meta-analysis. J Rheum Dis 24:293–302

    Article  Google Scholar 

  4. Choi HK, Curhan G (2010) Coffee consumption and risk of incident gout in women: the nurses’ health study. Am J Clin Nutr 92:922–927

    Article  CAS  Google Scholar 

  5. Graham D (1978) Caffeine—its identity, dietary sources, intake and biological effects. Nutr Rev 36:97–102

    Article  CAS  Google Scholar 

  6. Cohen NP, Foster RJ, Mow VC (1998) Composition and dynamics of articular cartilage: structure, function, and maintaining healthy state. J Orthop Sports Phys Ther 28:203–215

    Article  CAS  Google Scholar 

  7. Luo H, Li J, Cao H, Tan Y, Magdalou J, Chen L, Wang H (2015) Prenatal caffeine exposure induces a poor quality of articular cartilage in male adult offspring rats via cholesterol accumulation in cartilage. Sci Rep 5:17746

    Article  CAS  Google Scholar 

  8. Tan Y, Liu J, Deng Y, Cao H, Xu D, Cu F, Lei Y, Magdalou J, Wu M, Chen L (2012) Caffeine-induced fetal rat over-exposure to maternal glucocorticoid and histone methylation of liver IGF-1 might cause skeletal growth retardation. Toxicol Lett 214:279–287

    Article  CAS  Google Scholar 

  9. Giustina A, Mazziotti G, Canalis E (2008) Growth hormone, insulin-like growth factors, and the skeleton. Endocr Rev 29:535–559

    Article  CAS  Google Scholar 

  10. Wong THT, Sui Z, Rangan A, Louie JCY (2017) Discrepancy in socioeconomic status does not fully explain the variation in diet quality between consumers of different coffee types. Eur J Nutr:1–9

  11. Burgess S, Daniel RM, Butterworth AS, Thompson SG, Consortium E-I (2014) Network Mendelian randomization: using genetic variants as instrumental variables to investigate mediation in causal pathways. Int J Epidemiol 44:484–495

    Article  Google Scholar 

  12. Lawlor DA (2016) Commentary: two-sample Mendelian randomization: opportunities and challenges. Int J Epidemiol 45:908–915

    Article  Google Scholar 

  13. Amin N, Byrne E, Johnson J, Chenevix-Trench G, Walter S, Nolte I, Vink J, Rawal R, Mangino M, Teumer A (2012) Genome-wide association analysis of coffee drinking suggests association with CYP1A1/CYP1A2 and NRCAM. Mol Psychiatry 17:1116–1129

    Article  CAS  Google Scholar 

  14. Cornelis MC, Byrne EM, Esko T, Nalls MA, Ganna A, Paynter N, Monda KL, Amin N, Fischer K, Renstrom F (2015) Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption. Mol Psychiatry 20:647–656

    Article  CAS  Google Scholar 

  15. Consortium a (2012) Identification of new susceptibility loci for osteoarthritis (arcOGEN): a genome-wide association study. Lancet 380:815–823

    Article  Google Scholar 

  16. Thorgeirsson TE, Gudbjartsson DF, Surakka I, Vink JM, Amin N, Geller F, Sulem P, Rafnar T, Esko T, Walter S (2010) Sequence variants at CHRNB3–CHRNA6 and CYP2A6 affect smoking behavior. Nat Genet 42:448–453

    Article  CAS  Google Scholar 

  17. Burgess S, Butterworth A, Thompson SG (2013) Mendelian randomization analysis with multiple genetic variants using summarized data. Genet Epidemiol 37:658–665

    Article  Google Scholar 

  18. Hartwig FP, Davies NM, Hemani G, Davey Smith G (2016) Two-sample Mendelian randomization: avoiding the downsides of a powerful, widely applicable but potentially fallible technique. Oxford University press, pp

  19. Pierce BL, Burgess S (2013) Efficient design for Mendelian randomization studies: subsample and 2-sample instrumental variable estimators. Am J Epidemiol 178:1177–1184

    Article  Google Scholar 

  20. Bowden J, Davey Smith G, Burgess S (2015) Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int J Epidemiol 44:512–525

    Article  Google Scholar 

  21. Burgess S, Thompson SG (2017) Interpreting findings from Mendelian randomization using the MR-Egger method. Eur J Epidemiol 32:377–389

    Article  Google Scholar 

  22. Bowden J, Davey Smith G, Haycock PC, Burgess S (2016) Consistent estimation in Mendelian randomization with some invalid instruments using a weighted median estimator. Genet Epidemiol 40:304–314

    Article  Google Scholar 

  23. Hemani G, Zheng J, Wade K, Elsworth B, Langdon R, Burgess S (2016) MR-Base: a platform for systematic causal inference across the phenome using billions of genetic associations. Biorxiv 16:78972

    Google Scholar 

  24. Egger M, Smith GD, Phillips AN (1997) Meta-analysis: principles and procedures. BMJ 315:1533–1537

    Article  CAS  Google Scholar 

  25. Cornelis M (2012) Coffee intake. Prog Mol Biol Transl Sci 108:293–322. 10.1016. B978–0–12-398397-8.00012-5

  26. Hill HA, Kleinbaum DG (2000) Bias in observational studies. Encyclopedia of Biostatistics

  27. Lee YH, Bae SC, Song GG (2013) Hepatitis B virus (HBV) reactivation in rheumatic patients with hepatitis core antigen (HBV occult carriers) undergoing anti-tumor necrosis factor therapy. Pp

  28. Smith GD, Ebrahim S (2008) Mendelian randomization: genetic variants as instruments for strengthening causal inference in observational studies

  29. Thompson JR, Minelli C, Bowden J, Del Greco FM, Gill D, Jones EM, Shapland CY, Sheehan NA (2017) Mendelian randomization incorporating uncertainty about pleiotropy. Stat Med 36:4627–4645

    Article  Google Scholar 

  30. Paaby AB, Rockman MV (2013) The many faces of pleiotropy. Trends Genet 29:66–73

    Article  CAS  Google Scholar 

  31. Smith GD, Ebrahim S (2004) Mendelian randomization: prospects, potentials, and limitations. Int J Epidemiol 33:30–42

    Article  Google Scholar 

  32. Burgess S, Dudbridge F, Thompson SG (2016) Combining information on multiple instrumental variables in Mendelian randomization: comparison of allele score and summarized data methods. Stat Med 35:1880–1906

    Article  Google Scholar 

  33. Swerdlow DI, Kuchenbaecker KB, Shah S, Sofat R, Holmes MV, White J, Mindell JS, Kivimaki M, Brunner EJ, Whittaker JC (2016) Selecting instruments for Mendelian randomization in the wake of genome-wide association studies. Int J Epidemiol 45:1600–1616

    Article  Google Scholar 

  34. Burgess S, Thompson SG, Collaboration CCG (2011) Avoiding bias from weak instruments in Mendelian randomization studies. Int J Epidemiol 40:755–764

    Article  Google Scholar 

Download references

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This research received no specific grants from any public, commercial, or not-for-profit sector funding agencies.

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  1. Department of Rheumatology, Korea University College of Medicine, Korea University Anam Hospital, 73, Inchon-ro, Seongbuk-gu, Seoul, 02841, South Korea

    Young Ho Lee

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Lee, Y.H. Investigating the possible causal association of coffee consumption with osteoarthritis risk using a Mendelian randomization analysis. Clin Rheumatol 37, 3133–3139 (2018). https://doi.org/10.1007/s10067-018-4252-6

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