Mendelian randomization analyses revealed that coffee consumption reduces gout risk independently of serum uric acid levels


Akiyoshi Nakayama, Yuya Shirai, Yusuke Kawamura, Yu Toyoda, Masahiro Nakatochi, Seiko Shimizu, Nariyoshi Shinomiya, Yukinori Okada, Hirotaka Matsuo

National Defense Medical College, Tokorozawa


The effects of coffee consumption on serum uric acid (SUA) levels and gout risk are controversial. There have hitherto been no reports based on mendelian randomization (MR) analysis of its effects that consider pleiotropy.

Here we performed the first MR analyses for coffee consumption on SUA levels and gout, with considering pleiotropy, across ancestry populations.

We used the following summary statistics of genome-wide association studies (gwass) from a japanese population: habitual coffee consumption (152,634 subjects), gout (3,053 cases and 4,554 controls), and SUA levels (121,745 subjects). In addition to fixed-effect inverse variance weighted meta-analysis (ivw), we performed a robust evaluation of heterogeneity and removed several instruments for reasons of possible pleiotropy. Previous european datasets were also re-evaluated while considering heterogeneity.

As results, habitual coffee consumption was significantly and inversely associated with gout (odds ratio [or] = 0.29, 95% confidence interval [95%ci] = 0.16 - 0.51, p = 1.9e-5) as random effect ivw (phet = 5.5e-19). Excluding pleiotropic instruments, the protective effect on gout was confirmed in fixed-effect ivw (or = 0.75, 95%ci = 0.58-0.97, p = 0.026) without heterogeneity (phet = 0.39). However, we observed no significance in the previous european datasets when considering heterogeneity. Associations were not observed in MR analyses between coffee consumption and SUA levels in either ancestry when considering pleiotropy. Multivariable MR analysis showed that increased coffee consumption significantly reduced gout risk, even after adjusting for SUA levels (or = 0.50, 95%ci = 0.31-0.81, p = 0.0046).

Therefore, with pleiotropy taken into account, our MR analyses revealed that coffee consumption can causally reduce gout risk, and that it may reduce gout risk independently of SUA levels.