Observational studies have identified gout patients are often comorbid with dyslipidemia. However, the relationship between dyslipidemia and gout is still unclear. We first performed Mendelian randomization (MR) to evaluate the causal effect of four lipid traits on gout and serum urate based on publicly available GWAS summary statistics (n ~100,000 for lipid, 69,374 for gout and 110,347 for serum urate). MR showed each standard deviation (SD) (~12.26 mg/dL) increase in HDL resulted in about 25% (95% CI 9.0%–38%, p = 3.31E−3) reduction of gout risk, with 0.09 mg/dL (95% CI: −0.12 to −0.05, p = 7.00E−04) decrease in serum urate, and each SD (~112.33 mg/dL) increase of TG was associated with 0.10 mg/dL (95% CI: 0.06–0.14, p = 9.87E−05) increase in serum urate. Those results were robust against various sensitive analyses. Additionally, independent effects of HDL and TG on gout/serum urate were confirmed with multivariable MR. Finally, mediation analysis demonstrated HDL or TG could also indirectly affect gout via the pathway of serum urate. In conclusion, our study confirmed the causal associations between HDL (and TG) and gout, and further revealed the effect of HDL or TG on gout could also be mediated via serum urate.

观察性研究已确定痛风患者通常伴有血脂异常。然而，血脂异常与痛风之间的关系尚不清楚。我们首先进行孟德尔随机化 (MR)，根据公开可用的 GWAS 汇总统计数据（脂质n ~100,000，痛风 69,374 和血清尿酸 110,347 ）评估四种脂质特征对痛风和血清尿酸的因果影响。MR 显示 HDL 的每个标准偏差 (SD) (~12.26 mg/dL) 导致 痛风风险降低约 25% (95% CI 9.0%–38%, p = 3.31E-3)，0.09 mg/dL （95% CI：-0.12 至 -0.05，p  = 7.00E-04）血清尿酸降低，TG 每增加一个 SD（~112.33 mg/dL）与 0.10 mg/dL（95% CI：0.06-）相关0.14, p = 9.87E-05) 血清尿酸增加。这些结果在各种敏感分析中都是稳健的。此外，多变量 MR 证实了 HDL 和 TG 对痛风/血清尿酸盐的独立影响。最后，中介分析表明 HDL 或 TG 也可以通过血清尿酸途径间接影响痛风。总之，我们的研究证实了 HDL（和 TG）与痛风之间的因果关系，并进一步揭示了 HDL 或 TG 对痛风的影响也可能通过血清尿酸介导。